Miracle-dz/UniFAR-FTUs huggingface dataset:
Unfavourable consequences of chronic cardiac HIF-1α stabilization.

AIMS The hypoxia-inducible factor-1 (HIF-1) is the master modulator of hypoxic gene expression. The effects of chronically stabilized cardiac HIF-1α and its role in the diseased heart are not precisely known. The aims of this study were as follows: (i) to elucidate consequences of HIF-1α stabilization in the heart; (ii) to analyse long-term effects of HIF-1α stabilization with ageing and the ability of the HIF-1α overexpressing hearts to respond to increased mechanical load; and (iii) to analyse HIF-1α protein levels in failing heart samples. METHODS AND RESULTS In a cardiac-specific HIF-1α transgenic mouse model, constitutive expression of HIF-1α leads to changes in capillary area and shifts the cardiac metabolism towards glycolysis with a net increase in glucose uptake. Furthermore, Ca(2+) handling is altered, with increased Ca(2)(+) transients and faster intracellular [Ca(2+)] decline. These changes are associated with decreased expression of sarcoplasmic/endoplasmic reticulum calcium ATPase 2a but elevated phosphorylation of phospholamban. HIF-1α transgenic mice subjected to transverse aortic constriction exhibited profound cardiac decompensation. Moreover, cardiomyopathy was also seen in ageing transgenic mice. In parallel, we found an increased stabilization of HIF-1α in heart samples of patients with end-stage heart failure. CONCLUSION Changes induced with transgenic cardiac HIF-1α possibly mediate beneficial effects in the short term; however, with increased mechanical load and ageing they become detrimental for cardiac function. Together with the finding of increased HIF-1α protein levels in samples from human patients with cardiomyopathy, these data indicate that chronic HIF-1α stabilization drives autonomous pathways that add to disease progression.
REEXPOSURE TO OKT3 IN RENAL ALLOGRAFT RECIPIENTS

Between 40% and 80% of patients treated with the monoclonal antibody OKT3 develop blocking antibody against its idiotypic region. Thus a major concern with the use of OKT3 as part of a baseline immunosuppressive regimen is that formation of blocking antibodies might preclude its subsequent use. Between 7/86 and 2/87, 32 patients received prophylactic OKT3 in addition to low-dose prednisone, azathioprine, and cyclosporine. Prophylactic OKT3 did not prevent rejection, as 21 of 32 patients studied developed rejection. Retreatment of 13 patients with OKT3 successfully reversed 12 rejections and lowered the number of T3-positive cells in spite of a low level of blocking antibody in two patients in this group. Of the patients analyzed, 38% developed blocking antibody on initial exposure to OKT3, but OKT3 reuse was denied only 4 patients due to the presence of these antibodies. Three of these had rejections reversed with steroids alone; the other patient lost the allograft. A high frequency of infectious complications occurred in the retreatment group, with viral infections predominating. Only one patient in the retreated group developed antibodies after the second use. Appearance of blocking antibodies after use of OKT3 as part of a baseline prophylactic immunosuppressive regimen did not significantly compromise access to OKT3 for treatment of subsequent rejection episodes, but multiple exposures to OKT3 did increase the frequency of infectious complications.
A Clinical and Biological Comparison Between Malignant Mixed Müllerian Tumors and Grade 3 Endometrioid Endometrial Carcinomas

Objective: To examine the clinicopathologic features, progression-free interval, and survival of patients with grade 3 endometrioid endometrial cancer (G3 EEC) and malignant mixed müllerian tumors (MMMTs). Akt, epidermal growth factor receptor (EGFR), and HER-2/neu expression in these histologic subtypes was also investigated. Associations between phosphorylated Akt and clinicopathologic features were tested. Methods: One hundred nineteen women whose conditions were diagnosed with MMMT or G3 EEC from January 1, 1990, to December 31, 2003, met inclusion criteria. Retrospective data review was performed. In addition, Akt and EGFR protein expression was measured in tissue samples using Western blotting and immunohistochemistry. Fluorescence in situ hybridization was used to assay HER-2/neu gene amplification. Results: Fifty-nine patients with MMMT and 60 patients with G3 EEC were identified. Patients with MMMT were older (P = 0.055), more likely to be African American (P = 0.049), have a family history of breast cancer (P = 0.039), have disease involving the uterine cervix (P = 0.007), and experience postoperative complications (P = 0.012). Patients with MMMT had a significantly shorter progression-free interval (23 vs 57 months, P = 0.001) and survival (55 vs 92 months, P = 0.001) than patients with G3 EEC. Grade 3 EEC and MMMT have significantly higher phospho-Akt levels than grade 1 EEC and normal controls. Phospho-Akt was associated with depth of myometrial invasion (r = 0.46, P = 0.05), but not with stage, lymph-vascular space invasion, or tumor size. The mesenchymal component of MMMT preferentially demonstrated EGFR expression relative to the epithelial component (45% vs 13%, P = 0.06). HER-2/neu amplification was observed in 1 of 37 samples. Conclusions: Improved therapy is warranted for both poorly differentiated EEC and MMMT. Recognition of similarities and differences between MMMT and other high-grade histologic types of uterine cancer may provide rationale for new treatment approaches possibly incorporating targeted biological therapies.
[Neuroimaging in Human Immunodeficiency Virus infection].

INTRODUCTION Central Nervous System (CNS) infection by Human Immunodeficiency Virus (HIV) occurs early in the course of the disease and is associated with changes that can reach any level of the neuroaxis. Neuroimaging plays an increasingly important role both in diagnosis and in longitudinal monitoring of these complications, which can be divided into three major categories: injuries directly associated with HIV, opportunistic infections and malignancies. OBJECTIVES To identify and to describe the neuroradiological changes found in a population of HIV positive patients. METHODS Retrospective study with analysis of clinical processes and review of neuroimaging studies of HIV positive patients admitted to the Centro Hospitalar de Coimbra - E.P.E. in the period between 1st January 2008 and 31st March 2011. RESULTS During the study period we identified 337 episodes of hospitalization of patients with HIV infection, accounting for a total of 196 patients. Of these, 88 underwent at least one neuroimaging examination, with a mean age of 47.1 (27-89) years, of which 75% were males. In 12.5% of the examinations we did not find any relevant changes. In 69.3% atrophy was observed, in 31.2% sequelae lesions with different aetiologies (vascular, infectious), and eight cases of HIV encephalitis were identified. In 19.3% of patients it was diagnosed the presence of an opportunistic infection (11 cases of toxoplasmosis, four of progressive multifocal leukoencephalopathy, one case of tuberculosis and one of neurosyphilis). There were also 10 cases with evidence of recent vascular lesions. Although considered in the differential diagnosis in some cases, in our sample we did not identify any case of tumours. CONCLUSIONS Recognition of CNS changes associated with HIV infection and of their imaging patterns is of critical importance to the establishment of the diagnosis and to the appropriate treatment. Advanced techniques of Magnetic Resonance Imaging may have an important role in this context.
Virulence of the Fungal Pathogen Candida albicans Requires the Five Isoforms of Protein Mannosyltransferases

ABSTRACT The PMT gene family in Candida albicans encodes five isoforms of protein mannosyltransferases (Pmt proteins Pmt1p, Pmt2p, Pmt4p, Pmt5p, and Pmt6p) that initiate O mannosylation of secretory proteins. We compared virulence characteristics of pmt mutants in two complex, three-dimensional models of localized candidiasis, using reconstituted human epithelium (RHE) and engineered human oral mucosa (EHOM); in addition, mutants were tested in a mouse model of hematogenously disseminated candidiasis (HDC). All pmt mutants showed attenuated virulence in the HDC model and at least one model of localized candidiasis. The pmt5 mutant, which lacks in vitro growth phenotypes, was less virulent in the EHOM and HDC assays but had no consistent phenotype in the RHE assay. In contrast, the pmt4 and pmt6 mutants were less virulent in the RHE and HDC assays but not in the EHOM assay. The results stress the contribution of all Pmt isoforms to the virulence of C. albicans and suggest that the importance of individual Pmt isoforms may differ in specific host niches. We propose that Pmt proteins may be suitable targets for future novel classes of antifungal agents.
Slowed nerve conduction with wrist flexion in carpal tunnel syndrome

Phalen's wrist flexion test may reproduce the sensory symptoms of carpal tunnel syndrome (CTS). We have used this test in conjunction with motor and sensory latency studies in 20 patients with symptomatic CTS in one or both hands. The test caused an increase in the motor or sensory latency in half the patients. In 2 patients the latencies were abnormal only after wrist flexion. The test may thus be useful in diagnosis of borderline cases.
Out-of-hospital cardiac arrest: racial differences in outcome in Seattle.

OBJECTIVES Out-of-hospital sudden cardiac arrest is a key area in which to study the dual problem of the poorer health status of minority populations and their poorer access to the health care system. We proposed to examine the relationship between race (Black/White) and survival. METHODS We determined the incidence and outcome of cardiac arrests in Seattle for which medical assistance was requested. RESULTS Over a 26-month period, the age-adjusted incidence of out-of-hospital cardiac arrest was twice as great in Blacks than in Whites (3.4 vs 1.6 per 1000 aged 20 and over). The initial resuscitation rate was markedly poorer in the Black victims (17.1% vs 40.7%), and rates of survival to hospital discharge were also lower in Blacks (9.4% vs 17.1%). Both effective initial resuscitation and survival were significantly related to White race following adjustment for other covariates. CONCLUSION The differences in outcomes were not fully explained by features of the collapse or relevant service factors. Possible explanations include delays in instituting therapy, less bystander-initiated cardiopulmonary resuscitation, poorer levels of health, and differences in the underlying cardiac disorders.
A wavelet based method for steady-state detection in anesthesia

With the recent concern on patient's outcome following general anesthesia, automatic control of drugs has been a field of interest. The Bispectral Index (BIS) is an EEG based hypnosis monitor, in current use at the operating theatre as a guiding tool for the anesthesiologist to titrate drugs, and prevent awareness. When trying to model a certain process, it's very important to obtain information of the system behavior under steady-state conditions. In this study the hypnotic and analgesic drugs' effect on the hypnosis index BIS was analyzed, in order to obtain steady-state information of the system response (inputs-output), and in the future model the drugs combined effect. A steady-state index was obtained using a wavelet analysis technique for trend detection. This tool may be used in the future to model the drug's combined effect on the hypnosis indices, and also to bring some insight on disturbances not related to drug changes.
Thermal stability and interaction with ferret inflammatory exudates of two clones of influenza virus of differing virulence for both ferrets and man.

Abstract After intranasal inoculation of ferrets with influenza virus the upper respiratory tract infection diminishes during the second day and the onset of this reduction occurs earlier for an attenuated clone (64d) than for a virulent clone (7a) of the recombinant virus A/PR/8/34-A/England/939/69 (H3N2). The relevance of pyrexia and the nasal inflammatory response to this reduction in infection has been investigated. Egg-grown Clone 64d was more thermobile than Clone 7a at normal and pyrexial temperatures when suspended in egg allantoic fluid or phosphate-buffered saline. However, in infected nasal washes, both clones were rapidly inactivated when the washes were incubated at these temperatures. In vitro tests showed that both clones adsorbed to the phagocytes of peritoneal exudates from uninfected ferrets and nasal inflammatory exudates of ferrets infected with both clones. About 90% of the virus was adsorbed after 30 min at 0° or 370° and only 2-14% of this was recovered after treatment with receptor-destroying enzyme followed by freeze-thawing the cells. In contrast, high recoveries (36-112% of that adsorbed) were obtained from red blood cells that were treated similarly. Significant differences were not detected between the clones in either adsorption by or recovery from phagocytes of the different types of exudates. Thus pyrexia and the nasal inflammatory cells probably play a major role in the reduction of nasal tract infection but, while pyrexia may have had some influence, no evidence was obtained to indicate that the cells contributed to the earlier reduction of Clone 64d.
Behavior-Dependent States of the Hippocampal Network Affect Functional Clustering of Neurons

Local versus distant coherence of hippocampal CA1 pyramidal cells was investigated in the behaving rat. Temporal cross-correlation of pyramidal cells revealed a significantly stronger relationship among local (<140 microm) pyramidal neurons compared with distant (>300 microm) neurons during non-theta-associated immobility and sleep but not during theta-associated running and walking. In contrast, cross-correlation between local pyramidal cell-interneuron pairs was significantly stronger than between distant pairs during theta oscillations but were similar during non-theta-associated behaviors. We suggest that network state-dependent functional clustering of neuronal activity emerges because of the differential contribution of the main excitatory inputs, the perforant path, and Schaffer collaterals during theta and non-theta behaviors.
Isolation and characterization of microsatellites from the tapeworm Echinococcus granulosus

The Echinococcus granulosus genome was searched for microsatellites using 8 different repeated oligonucleotides as probes (GT15, CT15, AT15, CG15, CAT10, CAA10, CGG10 and CATA10). Southern blot experiments revealed that DNA regions containing GT, CAA, CATA and CT repeats are the most frequent in the E. granulosus genome. AT and CG probes showed no hybridization signal. Two loci containing CA/GT (Egmsca1 and Egmsca2) and 1 locus containing GA/CT (Egmsga1) repeats were cloned and sequenced. The locus Egmsca1 was analysed in 73 isolates from Brazil and Argentina whose strains were previously characterized. Brazilian isolates from cattle strain and Argentinean isolates from camel strain were monomorphic and shared the allele (CA)7. Argentinean isolates of sheep and Tasmanian sheep strains shared 2 alleles [(CA)8 and (CA)10] with Brazilian isolates of sheep strain. The allele (CA)11 was found only in Brazilian isolates of sheep strain at a low frequency. The Brazilian and the Argentinean sheep strain populations were tested for the Hardy-Weinberg equilibrium, and only the former was in agreement with the expectations. No polymorphism was found among individual protoscoleces from a single hydatid cyst, validating the utilization of pooled protoscoleces from 1 cyst, grouped as an isolate, in population studies. This work describes for the first time the isolation and characterization of microsatellites from E. granulosus.
Infants Perceive Spatial Structure Specified by Line Junctions

Lines in drawings can be perceived as the corners where surfaces intersect, outer boundaries of surfaces, or as markings on a surface. In this study infants' ability to distinguish between lines that indicate corners and edges and lines that indicate markings was investigated. Infants aged 7.5 months were habituated to line displays in which the lines specified a three-dimensional cube or two overlapping rectangles. Both displays contained lines indicating corners, edges, and surface markings. After habituation, infants viewed two test displays, one in which the corners or edges were deleted and one in which the surface markings were deleted. Infants looked significantly longer at the displays that lacked the corners or edges. The results suggest that infants attend to lines that depict corners and edges to a greater degree than they attend to lines that depict markings. Infants may do so because corners and edges specify the shapes of objects whereas markings do not.
Socioeconomic Differentials in Immune Response

Background: Lower socioeconomic status (SES) is strongly linked to health outcomes, though the mechanisms are poorly understood. Little is known about the role of the immune system in creating and sustaining health disparities. Here we test whether SES is related to cell-mediated immunity, as measured by the host's ability to keep persistent cytomegalovirus (CMV) antibody levels in a quiescent state. Methods: Censored regression models were used to test the cross-sectional relationship of education, income, and race/ethnicity with antibody response to CMV, using a nationally representative sample of 9721 respondents aged 25 years and older in the Third National Health and Nutrition Examination Survey (NHANES III, 1988–1994). Results: Among CMV-seropositive respondents, those with less education, lower income, and nonwhite race/ethnicity had higher levels of CMV antibodies at all ages. On average, each additional year of age was associated with CMV antibody levels that were 0.03 units higher (95% confidence interval = 0.03 to 0.04), whereas each additional year of education was associated with antibody levels that were 0.05 units lower (0.02 to 0.09). A doubling of family income was associated with antibody levels that were 0.25 units lower (0.11 to 0.39), the equivalent of 8 fewer years of age-related CMV antibody response. These relationships remained strong after controlling for baseline health conditions, smoking status, and BMI. Conclusions: SES is associated with an indirect marker of cell-mediated immunity in a nationally representative sample. SES differences in immune control over CMV may have fundamental implications for health disparities over the life course.
Volatile anaesthetics inhibit a cyclic AMP‐dependent sodium‐potassium current in cultured sensory neurones of bullfrog

1 Cultured dorsal root ganglion cells of the bullfrog were voltage‐clamped in the whole‐cell configuration. 2 An adenosine 3′:5′‐cyclic monophosphate (cyclic AMP)‐dependent cationic inward rectifier (IH) was inhibited by bath application of enflurane (0.2‐0.8 mm) and halothane (0.2‐0.5 mm), which thereby induced an outward current at the resting potential, and a membrane hyperpolarization in undamped cells. 3 The main effect of enflurane (0.5 mm) was to displace the steady‐state IH activation curve to a hyperpolarizing direction by about 10 mV, as well as to reduce the maximum H‐conductance to about 20%. 4 Forskolin (1–10 μm), which enhances IH by producing a depolarizing shift in the IH activation curve and increasing the maximum H‐conductance, recruited IH even when the current had already been eliminated by enflurane (1 mm).
HIV increases the risk of malaria in women of all gravidities in Kisumu, Kenya

Objective: To study the importance of HIV infection for malaria in pregnancy in Kisumu, Kenya. Subjects and methods: Healthy women with an uncomplicated pregnancy of 32 weeks or more attending the prenatal clinic in the Provincial Hospital between June 1996 and March 1999 were tested for HIV and malaria after consent had been obtained. For participating women who delivered in the same hospital, a blood smear of the mother and the placenta were obtained. Results: In the third trimester, 5093 women consented to testing: the prevalence of malaria and HIV was 20.1 and 24.9%, respectively. Among the 2502 screened women who delivered in the hospital, the prevalence of HIV, peripheral parasitaemia and placental malaria was 24.5, 15.2, and 19.0%, respectively. Compared with HIV-seronegative women, HIV-seropositive women were more likely to be parasitaemic, to have higher parasite densities, and to be febrile when parasitaemic. Placental infections in HIV-seropositive women were more likely to be chronic, as indicated by the presence of moderate to heavy pigment depositions. When adjusted by age, the typical gravidity-specific pattern of malaria in pregnancy disappeared in HIV-seropositive women; HIV-seropositive primigravidae had a similar risk of malaria as HIV-seropositive multigravidae. The excess malaria attributable to HIV in the third trimester increased from 34.6% among HIV-seropositive primigravidae, to 41.5% among HIV-seropositive secundigravidae, and 50.7% among HIV-seropositive gravidae with three or more pregnancies. Conclusion: HIV infection alters patterns of malaria in pregnant women; in areas with both infections, all pregnant women should use malaria prevention.
Optical tomography in two dimensions.

We consider in two dimensions, the inverse boundary problem of reconstructing the absorption and scattering coefficient of an inhomogeneous medium by probing it with diffuse light. The problem is modeled as an inverse boundary problem for the stationary linear Boltzmann equation. The information is encoded in the albedo operator. We show that we can recover the absorption and the scattering kernel from this information provided that the latter is small in an appropriate topology. We also give stability estimates and propose an approximate reconstruction procedure.
Translation can affect the antisense activity of RNase H1-dependent oligonucleotides targeting mRNAs

Abstract RNase H1-dependent antisense oligonucleotides (ASOs) can degrade complementary RNAs in both the nucleus and the cytoplasm. Since cytoplasmic mRNAs are actively engaged in translation, ASO activity may thus be affected by translating ribosomes that scan the mRNAs. Here we show that mRNAs associated with ribosomes can be cleaved using ASOs and that translation can alter ASO activity. Translation inhibition tends to increase ASO activity when targeting the coding regions of efficiently translated mRNAs, but not nuclear non-coding RNAs or less efficiently translated mRNAs. Increasing the level of RNase H1 protein eliminated the enhancing effects of translation inhibition on ASO activity, suggesting that RNase H1 recruitment to ASO/mRNA heteroduplexes is a rate limiting step and that translating ribosomes can inhibit RNase H1 recruitment. Consistently, ASO activity was not increased by translation inhibition when targeting the 3′ UTRs, independent of the translation efficiency of the mRNAs. Contrarily, the activity of 3′ UTR-targeting ASOs tended to be reduced upon translation inhibition, likely due to decreased accessibility. These results indicate that ASO activity can be affected by the translation process, and the findings also provide important information toward helping better ASO drug design.
Antifibrotic activity of rofecoxib in vivo is associated with reduced portal hypertension in rats with carbon tetrachloride‐induced liver injury

Background and Aim: Upregulation of cyclooxygenase‐2 (COX‐2), an inducible enzyme that is actively involved in inflammation and wound healing, has been found in cirrhotic livers. The aim of this study was to investigate the effects of selective inhibition of COX‐2 on the development of liver cirrhosis and portal hypertension in rats.