Miracle-dz/UniFAR-FTUs huggingface dataset:
Dendritic Cells Present Lytic Antigens and Maintain Function throughout Persistent γ-Herpesvirus Infection1

The activation and maintenance of Ag-specific CD8+ T cells is central to the long-term control of persistent infections. These killer T cells act to continuously scan and remove reservoirs of pathogen that have eluded the acute immune response. Acutely cleared viral infections depend almost exclusively on dendritic cells (DC) to present Ags to, and to activate, the CD8+ T cell response. Paradoxically, persistent pathogens often infect professional APCs such as DC, in addition to infecting a broad range of nonprofessional APC, raising the possibility that many cell types could present viral Ags and activate T cells. We addressed whether in persistent viral infection with murine gammaherpesviruses, DC or non-DC, such as B cells and macrophages, were required to maintain the continued activation of Ag-specific CD8+ T cells. We found that presentation of the surrogate Ag, OVA, expressed under a lytic promoter to CD8+ T cells during persistent infection was largely restricted to DC, with little contribution from other lymphoid resident cells, such as B cells. This is despite the fact that B cells harbor a very large reservoir of latent virus. Our results support that, during persistent viral infection, continual presentation of lytic Ags by DC leads to T cell activation critical for maintaining CD8+ T cells capable of limiting persistent viral infection.
Contraceptive choice for young people

Background and methodology Giving young women access to newer contraceptives such as the combined contraceptive patch, combined contraceptive vaginal ring and single-rod implant may help reduce teenage pregnancies. However, little is known about young people's attitudes towards these contraceptives. This cross-sectional survey, using a self-completion questionnaire, aimed to explore young people's attitudes towards these contraceptives in order to develop understanding of the choices they make about contraception. Participants were a self-selecting sample of young women attending contraception clinics in Newcastle upon Tyne, UK. Statistical analysis was carried out using appropriate univariate tests. Qualitative analysis involved identification of key themes, which were continuously challenged by looking for conformity and variation and by identifying disconfirming cases. Results The majority of the 127 participants had no prior knowledge of the patch, vaginal ring or implant. Interest in using these contraceptives was low. Associations were found between their attitude towards using them and the participants' age, experience of pregnancy scares, experience of unplanned pregnancies and prior knowledge of the contraceptives. Six major themes emerged relating to the advantages and disadvantages of these contraceptives and included convenience, effectiveness, safety along with side effects, invasiveness and discretion. Discussion and conclusions Young people's knowledge of and attitudes towards these contraceptives was variable and may have been influenced by experience and access to information. Themes identified from perceptions of these contraceptives are useful in developing understanding of what young people look for in contraceptives. Health professionals should provide information on these themes when assisting young people in making informed decisions about contraception.
α-Linolenic Acid Reduces Growth of Both Triple Negative and Luminal Breast Cancer Cells in High and Low Estrogen Environments

Flaxseed, rich in α-linolenic acid (ALA), is a complementary breast cancer (BC) therapy; however ALA effectiveness and mechanism are unclear. Variation in cellular expression of estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2), and estrogen (E2) levels may alter ALA effectiveness. This research determined the effect of ALA on growth, apoptosis, and phospholipid fatty acids of 4 BC cell lines with varying receptor expression ± E2. MCF-7 (ER+/PR+/HER2-), BT-474 (ER+/PR+/HER2+), MDA-MB-231 (ER-/PR-/HER2-) and MDA-MB-468 (ER-/PR-/HER2-) cells were incubated with ALA (50–200 μM) ± 1 nM E2 for 48–72 h. ALA dose-dependently reduced growth, measured by trypan blue exclusion, of all cells (55–80% with 75 μM), and this effect was not altered by E2. ALA (75 μM)+E2 induced apoptosis, measured by flow cytometry (up to 111.2%). Decreased growth and increased apoptosis is related to increased cell phospholipid % ALA (up to 25.1%), measured by gas chromatography. ALA is shown for the first time to reduce cell growth and induce apoptosis regardless of receptor expression and E2 environment, by incorporating into BC phospholipids, supporting the use of ALA and ALA-rich foods as a safe, inexpensive complementary therapy for a wide range of BC.
Gestion et enjeux des espaces urbains à risque d'origine naturelle : les versants et les quebradas de Quito, Equateur

Analyse geographique et politique du risque d'origine naturelle en milieu urbain, cette these traite de l'espace a risque et de sa gestion. Le site choisi est la ville de quito en equateur. Celle-ci concentre a la fois un large eventail d'aleas naturels (sismiques, volcaniques et morphoclimatiques) et des enjeux lies aux caracteristiques d'une metropole d'etat. Les autorites locales ont elabore depuis le debut des annees quatre-vingt des politiques de lutte contre ces risques. Or, la municipalite concentre ces efforts sur le risque d'inondation, le moins meurtriers. A cette fin, les quebradas et les versants nord-occidentaux de la ville recoivent un traitement privilegie alors que la geographie physique et humaine montrent que c'est le fond de la gouttiere et les versants centraux et sud-orientaux qui sont les espaces a risque majeur. Pourquoi cette distinction spatiale ? a partir de ce decalage entre une realite geographique et les representations sociales du risque, l'analyse revele des enjeux majeurs de la societe quitenienne : la mobilite et le developpement du reseau d'egouts apparaissent alors comme les veritables determinants de la lutte contre le risque et de la definitiondes espaces a risques. Enfin, les chantiers mis en oeuvre pour lutter contre les risques d'inondation apparaissent comme un moyen pour la municipalite de maitriser des espaces qui echappent a son oeuvre planificatrice et revelent les enjeux lies aussi bien a la maitrise de l'urbanisation qu'au developpement de la decentralisation de l'etat vers la municipalite. Combinant l'etude des representations socio-spatiales du risque et l'utilisation des donnees geographique physiques et humaines, cette recherche a eu pour but de demontrer la necessite d'introduire la notion d'enjeu dans la definition du risque et celle de marge dans la definition de l'espace a risque.
Physiological Responses to Psychological Challenge under Hypnosis in Patients Considered to Have the Hyperventilation Syndrome: Implications for Diagnosis and Therapy

Thirty patients who were considered to have the hyperventilation syndrome on clinical grounds (history and observation) were referred for testing: 29 patients completed a forced hyperventilation provocation test, and 28 underwent hypnosis during which time a psychological challenge was introduced which was meaningful to each individual patient. In 19/27 of these patients the PetCO2 fell by an average of 18.2 mmHg and persisted spontaneously for more than three minutes. In 10 normal controls studied in a similar fashion there was an average fall of 5 mmHg. The difference in response between responders and controls/non-responders was highly significant (P< 0.001). A review of the literature is presented, for comparison. It is considered that a psychological challenge under hypnosis may have important implications for diagnosis and therapy in some patients considered to have the hyperventilation syndrome.
Visual impairment in Swedish children. III. Diagnoses.

PURPOSE To gain an overview of the spectrum of diagnoses among Swedish visually impaired children. METHODS An epidemiological study of all known visually impaired children was made by review of medical records. RESULTS AND CONCLUSION In all we found 2373 children, 0-19 years of age, with an age-specific prevalence of 10.9/10,000. The two largest diagnostic groups included neuro-ophthalmological and retinal diseases. The most frequent disorders were cerebral visual impairment, non-hereditary optic atrophy, retinal dystrophy (when regarded as a general entity), congenital hypoplasia of the optic nerve and congenital cataract. Nystagmus secondary to brain disorder, albinism, congenital nystagmus, retinopathy of prematurity and high myopia were also found in a considerable number of patients. The leading diagnoses in children with WHO-defined childhood blindness were non-hereditary optic atrophy, cerebral visual impairment and retinopathy of prematurity. A large proportion of the children, especially in the groups with neuro-ophthalmological disorders and malformations of the posterior segment had additional impairments, emphasizing the importance of a multi-disciplinary approach when assessing multi-handicapped children.
[Stereochemistry of benzanilides and N-methylbenzanilides].

Conformations of benzanilide , N-methylbenzanilide and those with a methyl group(s) ortho to the amide bond in solution and in the crystal have been studied. N-Methylbenzanilide exists in cis-amide (E) form in the crystal. In CDCl3 solution, cis-amide form is also predominant (99%), while benzanilide exists in trans-amide (Z) form in the crystal and in solution. In the crystal, all the methyl-substituted benzanilides exist in trans-amide conformation and the introduction of an ortho-methyl group(s) makes the interplanar angles of the aromatic rings and the amide group (Aramide) larger. N-Methylbenzanilides exist in cis form in the crystal except the compound which has four methyl groups ortho to the amide bond. For the N-methylbenzanilides, the effects of introduction of one or two ortho-methyl groups on the dihedral angles of Ar-amide are smaller than that for the secondary benzanilides. In solution, benzanilides exist exclusively in trans conformation except for the compound 12 which has a minor cis conformer (3%) in CDCl3, whereas N-methylbenzanilides exist in equilibrium between the major cis-form and the minor trans-form. The tetramethyl derivative exists in trans conformation in solution as observed in the crystal. For N-methylbenzanilides, an introduction of a methyl group(s) ortho to the amide bond seems to destabilize the cis-amide conformation in solution, resulting in an increased ratio of the trans-amide conformation.
Predictive value of adiponectin in patients with multivessel coronary atherosclerosis detected on computed tomography angiography.

AIM Multislice computed tomography coronary angiography (CTCA) can be used to detect coronary plaques that predict the risk of cardiovascular events. This study aimed to identify the risk factors associated with the extent of coronary plaques detected using CTCA and to determine the value of adiponectin measurement for identifying high-risk patients with multivessel coronary atherosclerosis. METHODS The study included 298 patients who underwent CTCA for coronary artery disease (CAD) screening between July 2008 and October 2011. We investigated the relationship between the extent of coronary atherosclerosis in terms of the number of diseased vessels and various risk factors, including the serum adiponectin level. RESULTS The adiponectin level was found to be significantly associated with multivessel coronary atherosclerosis in a univariate analysis (p=0.001). A multivariate analysis revealed the adiponectin level to also be significantly associated with multivessel coronary atherosclerosis (p=0.01), independent of other significant risk factors, including an advanced age, male gender, diabetes mellitus (DM) and hypertension (HT). A receiver operating characteristic curve analysis revealed that a combination of these factors significantly predicted multivessel coronary atherosclerosis (area under the curve, 0.73;95% confidence interval, 0.67-0.78). As the number of these factors increased, the proportion of patients with multivessel coronary atherosclerosis increased, while the proportion of patients with normal coronary arteries decreased (p < 0.0001). CONCLUSIONS A low adiponectin level combined with an advanced age, male gender, DM, and HT is independently and incrementally associated with multivessel coronary atherosclerosis. The number of factors may predict the extent of coronary atherosclerosis in patients without documented CAD.
Functional Up-regulation of HERG K+ Channels in Neoplastic Hematopoietic Cells*

Kv1.3 channels regulate proliferation of normal lymphocytes, but the role of voltage-gated potassium channels in transformed hematopoietic cells is not known. We examined transcripts for Kv1.3, h-erg, h-eag, andBEC1 genes in primary lymphocytes and leukemias and in several hematopoietic cell lines. Surprisingly, BEC1, formerly thought to be brain-specific, was present in all the primary leukemias examined, in resting peripheral blood lymphocytes, and in proliferating activated tonsillar cells, lymphocytes from Sjögren's patients, and Epstein-Barr virus-transformed B-cells. Only h-erg mRNA was up-regulated in the cancer cells, but this was not due to proliferation per se, because it was not elevated in any of the proliferating noncancerous lymphocyte types examined. Nor did h-erg transcript levels correlate with the B-cell subset, because it was elevated in immature neoplastic B-CLL cells (CD5+) and in a CD5− Burkitt's lymphoma cell line (Raji) but not in Sjögren's syndrome cells (enriched in CD5+ B-cells) or Epstein-Barr virus-transformed B-cells, which are mature CD5− B-cells. The protein and whole cell current levels roughly corresponded with the amount of mRNA expressed in three hematopoietic cell lines: CEM (an acute lymphoblastic leukemic line), K562 (a chronic myelogenous leukemic line), and U937 (an acute promyelocytic leukemic line). The selective HERG channel blocker, E-4031, reduced proliferation of CEM, U937, and K562 cells, and this appears to be the first direct evidence of a functional role for the HERG current in cancer cells. Selective up-regulation of h-erg appears to occur in neoplastic hematopoietic cells, thus providing a marker and potential therapeutic target.
Impact of Mutations in the Coreceptor Binding Site on Human Immunodeficiency Virus Type 1 Fusion, Infection, and Entry Inhibitor Sensitivity

ABSTRACT An increasingly large number of antiviral agents that prevent entry of human immunodeficiency virus (HIV) into cells are in preclinical and clinical development. The envelope (Env) protein of HIV is the major viral determinant that affects sensitivity to these compounds. To understand how changes in Env can impact entry inhibitor sensitivity, we introduced six mutations into the conserved coreceptor binding site of the R5 HIV-1 strain YU-2 and measured the effect of these changes on CD4 and coreceptor binding, membrane fusion levels and rates, virus infection, and sensitivity to the fusion inhibitors enfuvirtide (T-20) and T-1249, the CCR5 inhibitor TAK-779, and an antibody to CD4. The mutations had little effect on CD4 binding but reduced CCR5 binding to various extents. In general, reductions in coreceptor binding efficiency resulted in slower fusion kinetics and increased sensitivity to TAK-779 and enfuvirtide. In addition, low CCR5 binding usually reduced overall fusion and infection levels. However, one mutation adjacent to the bridging sheet β21 strand, P438A, had little effect on fusion activity, fusion rate, infectivity, or sensitivity to enfuvirtide or T-1249 despite causing a marked reduction in CCR5 binding and a significant increase in TAK-779 sensitivity. Thus, our findings indicate that changes in the coreceptor binding site of Env can modulate its fusion activity, infectivity, and entry inhibitor sensitivity by multiple mechanisms and suggest that reductions in coreceptor binding do not always result in prolonged fusion kinetics and increased sensitivity to enfuvirtide.
Postembryonic development of corazonin‐containing neurons and neurosecretory cells in the blowfly, Phormia terraenovae

An antiserum against the cockroach cardioactive peptide corazonin was used to investigate the distribution of immunoreactive neurons and neurosecretory cells in the nervous system of the blowfly, Phormia terraenovae, during postembryonic development. A small number of corazonin‐immunoreactive neurons was found at larval, pupal, and adult stages. At all postembryonic stages two cell groups were found in the protocerebrum of the brain: (1) two lateral cell clusters and (2) two median cells. In the larva eight bilateral cell pairs were found in thoracic and abdominal neuromeres of the fused ventral ganglion. The lateral brain neurons are located in the lateral neurosecretory cell group and extend axons with branches in several components of the retrocerebral neuroendocrine complex, in the stomatogastric nervous system of larvae and adults, and additionally in muscles of the alimentary canal in the adult. The most prominent element of these peripheral processes is a large plexus of varicose fibers located in the wall of the aorta, the main site for the release of neurohormones produced in the brain of blowflies. The presence of corazonin‐immunoreactive material in the aortic plexus suggests that this peptide functions as a neurohormone, During metamorphosis, the immunoreactive neurons found in the thoracic‐abdominal ganglion of the larva disappear, and in the brain new immunoreactive neurons are added to those that persist from larval stages. The bulk of the corazonin‐immunoreactive material extracted from adult brains and corpora cardiaca‐aorta complexes was found to co‐elute with synthetic corazonin in reversed‐phase high‐performance liquid chromatography as monitored with enzyme‐linked immunosorbent assay. © 1994 Wiley‐Liss, Inc.
Topographic assessment of human enamel surface treated with different topical sodium fluoride agents: Scanning electron microscope consideration

Introduction: Continuous balanced demineralization and remineralization are natural dynamic processes in enamel. If the balance is interrupted and demineralization process dominates, it may eventually lead to the development of carious lesions in enamel and dentine. Fluoride helps control decay by enhancing remineralization and altering the structure of the tooth, making the surface less soluble. Methodology: One hundred and twenty sound human permanent incisors randomly and equally distributed into six groups as follows: Group I - Control, II - Sodium fluoride solution, III - Sodium fluoride gel, IV - Sodium fluoride varnish, V - Clinpro Tooth Crème (3M ESPE), and VI-GC Tooth Mousse Plus or MI Paste Plus. The samples were kept in artificial saliva for 12 months, and the topical fluoride agents were applied to the respective sample groups as per the manufacturer instructions. Scanning electron microscope (SEM) evaluation of all the samples after 6 and 12 months was made. Results: Morphological changes on the enamel surface after application of fluoride in SEM revealed the presence of globular precipitate in all treated samples. Amorphous, globular, and crystalline structures were seen on the enamel surface of the treated samples. Clear differences were observed between the treated and untreated samples. Conclusion: Globular structures consisting of amorphous CaF2precipitates, which acted as a fluoride reservoir, were observed on the enamel surface after action of different sodium fluoride agents. CPP-ACPF (Tooth Mousse) and Tricalcium phosphate with fluoride (Clinpro tooth crème) are excellent delivery vehicles available in a slow release amorphous form to localize fluoride at the tooth surface.
Optimized Fast Dynamic Contrast-Enhanced Magnetic Resonance Imaging of the Prostate: Effect of Sampling Duration on Pharmacokinetic Parameters

ObjectiveThe aim of this study was to evaluate the effect of sampling duration on pharmacokinetic parameters from dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI) and their diagnostic accuracy regarding the detection of potentially malignant prostate lesions. Materials and MethodsSixty-six consecutive male patients (mean [SD] age, 65.4 [10.8] years) with clinically suspected prostate cancer were included. All patients underwent multiparametric MRI of the prostate (T2-weighted imaging, diffusion-weighted imaging, and DCE-MRI) on a 3 T MRI scanner. Patients were divided into 2 groups depending on the prostate imaging reporting and data system (PI-RADS) score of the detected lesions (group A: PI-RADS ⩽3, n = 32; group B: PI-RADS >3, n = 34). In all patients, DCE-MRI was performed using a CAIPIRINHA-Dixon-TWIST volume interpolated breath-hold examination sequence (spatial resolution, 3 × 1.2 × 1.2 mm; temporal resolution, 5 seconds; total sampling duration, 4:10 minutes [250 seconds]) with body weight–adapted administration of contrast agent (gadobutrol, Bayer Healthcare, Berlin, Germany). Five DCE-MRI series with different acquisition durations ranging from 50 to 250 seconds were retrospectively generated from the original data sets. Pharmacokinetic parameters (ie, Ktrans, Kep, Ve, and iAUC60) were calculated for the different sampling durations using the Tofts model. Both lesion groups and all 5 DCE-MRI series were compared regarding pharmacokinetic parameters. Diagnostic accuracy for the detection of potentially malignant lesions was calculated for all 5 series using receiver operating characteristic analysis. ResultsFor all 5 series, Ktrans, Kep, and iAUC60 in patient group B were significantly higher than the respective parameters in patient group A (all P ⩽ 0.008). In both groups, Ktrans, Kep, and iAUC60 remained constant at 200 and 150 seconds acquisition duration and did not significantly differ from parameters estimated from the original data sets (250 seconds; all P ≥ 0.310). Ve did not differ significantly between the 2 groups (P ≥ 0.337) and acquisition time did not have a significant effect on this parameter (P ≥ 0.275). Receiver operating characteristic analyses showed consistent diagnostic accuracy for the different series; only diagnostic accuracy of Kep decreased with lowered sampling duration, showing lowest accuracy for the 50-second series (0.682; 95% confidence interval, 0.553–0.811). ConclusionsUsing fast optimized DCE-MRI of the prostate, a minimum sampling duration of 150 seconds is required for sufficient pharmacokinetic parameter estimates, providing a high diagnostic accuracy regarding the discrimination between benign and potentially malignant lesions.