Miracle-dz/UniFAR-FTUs huggingface dataset:
Functional competence of T cells in the absence of glycosylphosphatidylinositol‐anchored proteins caused by T cell‐specific disruption of the Pig‐agene

T lymphocytes express various glycosylphosphatidylinositol (GPI)‐anchored surface proteins, such as Thy‐1 and Ly‐6A. However, functional contribution of GPI‐anchored proteins in T cell activation is as yet poorly understood. Here we report the generation of mutant mice deficient in the expression of GPI‐anchored molecules exclusively in their T cells. We established mice carrying three identically oriented lox‐P sites within the Pig‐a gene, which encodes a component essential for the initial step of GPI anchor biosynthesis. These mice were crossed with mice carrying the Cre recombinase gene driven by the T cell‐specific p56lck proximal promoter. Offspring carrying both the lox‐P ‐containing Pig‐a gene and the Cre transgene exhibited almost complete loss of the surface expression of GPI‐anchored molecules on peripheral T cells. Interestingly, those T cells deficient in GPI‐anchored mole cules were capable of responding to T cell receptor stimulation in vitro and in vivo. These results indicate that T cells lacking the expression of GPI‐anchored molecules are functionally competent in exerting TCR‐mediated immune responses.
Patients' Experiences of Nurse-Led Screening for Cardiovascular Risk in Rheumatoid Arthritis.

BACKGROUND Patients with rheumatoid arthritis (RA) have increased morbidity and mortality due to cardiovascular disease (CVD). Screening for cardiovascular risk is recommended by the European League Against Rheumatism (EULAR). There is a lack of evidence of the experiences of RA patients who are screened for CVD. Such information is important in order to organize and further develop screening programmes for CVD in patients with RA. The aim of the present study was to explore RA patients' experiences of participation in nurse-led screening for CVD and to identify key issues for the future organization of screening programmes. METHODS Three qualitative focus group interviews were carried out with 14 outpatients diagnosed with RA. The participants were stratified into groups, depending on whether they had a low-to-moderate or high ten-year risk of cardiovascular death according to the European Systematic Coronary Risk Evaluation (SCORE) system. Data were analysed using meaning condensation to identify key themes. RESULTS Five themes were identified: reactions to receiving the invitation to the screening consultation; screening consultation adapted to needs and RA; duration reflected needs; screening consultation brought a sense of relief; and motivation and sense of control. Regardless of their CV risk, the participants found it important that the screening consultation was adapted to their needs and their illness as RA had a major impact on their daily life. CONCLUSIONS When planning future screening programmes for CVD for patients with RA, it is important that the screening consultation is individualized and tailored to patients' needs and their RA. Copyright © 2015 John Wiley & Sons, Ltd.
D2 receptors receive paracrine neurotransmission and are consistently targeted to a subset of synaptic structures in an identified neuron of the crustacean stomatogastric nervous system

Dopamine (DA) modulates motor systems in phyla as diverse as nematodes and arthropods up through chordates. A comparison of dopaminergic systems across a broad phylogenetic range should reveal shared organizing principles. The pyloric network, located in the stomatogastric ganglion (STG), is an important model for neuromodulation of motor networks. The effects of DA on this network have been well characterized at the circuit and cellular levels in the spiny lobster, Panulirus interruptus. Here we provide the first data about the physical organization of the DA signaling system in the STG and the function of D2 receptors in pyloric neurons. Previous studies showed that DA altered intrinsic firing properties and synaptic output in the pyloric dilator (PD) neuron, in part by reducing calcium currents and increasing outward potassium currents. We performed single cell reverse transcriptase‐polymerase chain reaction (RT‐PCR) experiments to show that PD neurons exclusively expressed a type 2 (D2αPan) DA receptor. This was confirmed by using confocal microscopy in conjunction with immunohistochemistry (IHC) on STG wholemount preparations containing dye‐filled PD neurons. Immunogold electron microscopy showed that surface receptors were concentrated in fine neurites/terminal swellings and vesicle‐laden varicosities in the synaptic neuropil. Double‐label IHC experiments with tyrosine hydroxylase antiserum suggested that the D2αPan receptors received volume neurotransmissions. Receptors were further mapped onto three‐dimensional models of PD neurons built from Neurolucida tracings of confocal stacks from the IHC experiments. The data showed that D2αPan receptors were selectively targeted to approximately 40% of synaptic structures in any given PD neuron, and were nonuniformly distributed among neurites. J. Comp. Neurol. 518:255–276, 2010. © 2009 Wiley‐Liss, Inc.
Saturated fats and blood lipids: new slant on an old story.

In recent years the association between dietary saturated fat, hypercholesterolemia, and coronary artery disease has been re-explored. Prompted largely by the notion that dietary fats, and their attendant fatty acids, can specifically influence the distribution of the plasma cholesterol between low density (LDL) and high density (HDL) lipoprotein cholesterol, the focus of the original research has shifted from total cholesterol to lipoproteins. Several new, sometimes controversial, concepts have arisen that challenge underlying assumptions of the Keys-Hegsted regression equations. First, although saturated fats as a class raise LDL, they also appear to have primary responsibility among dietary fatty acids for raising HDL, possibly depending on a balanced intake of polyunsaturated fats. Second, not all saturated fatty acids are equally responsible for changes in LDL or HDL. Only natural triglycerides (TG) rich in lauric (12:0) and myristic (14:0) acids are especially cholesterolemic, whereas 16:0-rich fats can be neutral or cholesterol-raising depending on the metabolic circumstances (lipoprotein setpoint) of the host. In normolipemic individuals with normal lipoprotein metabolism, dietary palmitic acid (16:0) typically appears neutral. When lipoprotein metabolism is impaired, eg, if LDL receptor activity is depressed by the presence of dietary cholesterol, consumption of 16:0-rich TGs can contribute to hypercholesterolemia. Although stearic acid (18:0) is typically considered neutral, exaggerated consumption of 18:0-rich fat (cocoa butter) lowers both LDL and HDL. Third, the saturated fat effect is related both to the dietary cholesterol load and the lipoprotein setpoint of the host, eg, 16:0 becomes progressively cholesterolemic as dietary cholesterol raises the setpoint. (ABSTRACT TRUNCATED AT 250 WORDS)
Bipolar disorder

INTRODUCTION Bipolar disorder, with mood swings between depression and mania, may affect up to 1.5% of adults, and increases the risk of suicide and disability. Most people improve over time, but two thirds may have residual dysfunction, and at least 40% may have recurrent episodes. METHODS AND OUTCOMES We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of treatments in people with mania associated with bipolar disorder? What are the effects of treatments in bipolar depression? What are the effects of interventions to prevent relapse of mania or bipolar depression? We searched: Medline, Embase, The Cochrane Library and other important databases up to July 2006 (Clinical Evidence reviews are updated periodically, please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA). RESULTS We found 60 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions. CONCLUSIONS In this systematic review we present information relating to the effectiveness and safety of the following interventions: antidepressants, carbamazepine, chlorpromazine, clonazepam, cognitive therapy, education, family-focused psychoeducation, gabapentin, haloperidol, lamotrigine, lithium, olanzapine, psychological treatments, quetiapine, risperidone, topiramate, valproate, and ziprasidone.
Neonatal Neurobehavioral Responses after Epidural Anesthesia for Cesarean Section Using Lidocaine and Bupivacaine

We compared the early neonatal neurobehavioral responses after lumbar epidural anesthesia for elective cesarean section using 2% lidocaine (n = 10) and 0.5% bupivacaine (n = 21). We tested the infants at 4 and 24 hr after birth and found that the neonates in the lidocaine group scored as well as those in the bupivacaine group on all parameters of the early neonatal neurobehavioral score (ENNS). In fact on one parameter, sucking response at 24 hr, the neonates in the lidocaine group scored significantly higher than those in the bupivacaine group. We concluded that 2% lidocaine does not compromise newborn outcome when compared to 0.5% bupivacaine and that it provides a satisfactory choice for use during elective cesarean section in healthy pregnancies. This conclusion is important in the light of the current concern over the safety of the use of chloroprocaine and bupivacaine in obstetric anesthesia.
Elective percutaneous dilatational tracheostomy. A new simple bedside procedure; preliminary report.

The development by the senior author (P.C.) of percutaneous tracheostomy from cricothyroidostomy and subcricoid fingertip tracheostomy is traced, and the technique and patient material of percutaneous subcricoid tracheostomy is presented. This new technique consists of inserting a tracheostomy tube by the use of a J guide wire inserted through a cannula into the tracheal lumen. Tapered dilators follow the guide wire and dilate the opening in the tracheal walls. A tracheostomy tube snugly fitted over a dilator is then passed into the trachea between the cricoid cartilage and the first tracheal ring. This procedure avoids the immediate and postoperative complications of "standard" tracheostomy. An experience of 134 tracheostomies of various types culminated in the development of the percutaneous technique. To date 26 such operations on 24 patients have been done with no significant complications due to the operation. The percutaneous technique should reduce the severity and incidence of intraoperative complications. Late complications, which have been no problem to date, are being evaluated with longer follow-up and with a greater patient population.
Conceptions of privacy and the non-disclosure of same-sex behaviour by behaviourally-bisexual men in heterosexual relationships

Little attention has been paid to why some behaviourally-bisexual men (i.e., men who have sex with both men and women) choose not to disclose their same-sex behaviour. Using Communication Privacy Management (CPM) theory, we report on the ways these men conceptualise their same-sex behaviour as private, and thus feel justified in not disclosing it to family, friends and female partners. In-depth interviews were conducted with an ethnically diverse sample of 203 non-disclosing behaviourally-bisexual men in New York City. The men offered a number of privacy rules to justify their non-disclosure, including: (1) their same-sex behaviours were their own business and nobody else's, (2) others had no reason to know, (3) the topic of sexual behaviour was too personal, (4) they were private people in general and (5) it was inappropriate to discuss same-sex behaviour in many contexts. Some privacy rules were used more often to justify non-disclosure to friends and family than to female partners. These findings provide insights into the reasons for non-disclosure among behaviourally-bisexual men, offer support for and extend CPM theory for the management of sexual information and offer insights into the importance of privacy for the design and delivery of health-promotion services for this population.
Management and outcome differences in supraglottic cancer between Ontario, Canada, and the Surveillance, Epidemiology, and End Results areas of the United States.

PURPOSE We compared the management and outcome of supraglottic cancer in Ontario, Canada, with that in the Surveillance, Epidemiology, and End Results (SEER) Program areas in the United States. METHODS Electronic, clinical, and hospital data were linked to cancer registry data and supplemented by chart review where necessary. Stage-stratified analyses compared initial treatment and survival in the SEER areas (n = 1,643) with a random sample from Ontario (n = 265). We also compared laryngectomy rates at 3 years in those patients 65 years and older at diagnosis. RESULTS Radical surgery was more commonly used in SEER, with absolute differences increasing with increasing stage: I/II, 17%; III, 36%; and IV, 45%. The 5-year survival rates were 74% in Ontario and 56% in SEER for stage I/II disease (P =.01), 55.7% in Ontario and 46.8% in SEER for stage III disease (P =.40), and 28.5% in Ontario and 29.1% in SEER for stage IV disease (P =.28). Cancer-specific survival results mirrored the overall survival results with the exception of stage IV disease, for which 34.6% of Ontario patients survived their cancer compared with 38.1% in SEER (P =.10). This stage IV difference was more pronounced when we further controlled for possible cause of death errors by restricting the comparison to patients with a single primary cancer (P =.01). Three-year actuarial laryngectomy rates differed. In stage I/II, these rates were 3% in Ontario compared with 35% in SEER (P < 10(-3)). In stage III disease, the rates were 30% and 54%, respectively (P =.03), and in stage IV disease they were 33% and 64% (P =.002). CONCLUSION There are large differences in the management of supraglottic cancer between the SEER areas of the United States and Ontario. Long-term larynx retention was higher in Ontario, where radiotherapy is widely regarded as the treatment of choice and surgery is reserved for salvage. In stages I to III, survival was similar in the two regions despite the differences in treatment policy. In stage IV, there may be a small survival advantage in the U.S. SEER areas related to the higher use of primary surgery.
Cyclooxygenase‐2 expression in experimental post‐transplant obliterative bronchiolitis

Epithelial cell injury, inflammation, progressive fibrosis, and airway obliteration are histological features of post‐transplant obliterative bronchiolitis (OB). Cyclooxygenase (COX)‐2 is expressed in acute and chronic inflammatory responses. Our aim was to elucidate the possible role of COX‐2 in post‐transplant OB by using a heterotopic bronchial porcine model. Bronchial allografts from non‐related donors were transplanted subcutaneously into 24 random‐bred domestic pigs, each weighing about 20 kg. Groups studied had grafts, non‐treated allografts, allografts given cyclosporine A (CsA), methylprednisolone (MP), and azathioprine (Aza), and allografts given CsA, MP, and everolimus. Grafts were serially harvested during a follow‐up period of 21 days for histology (H&E) and immunohistochemistry. Immunostaining was performed with monoclonal IgG against human COX‐2 peptide, and histological alterations and immunohistochemical positivity were graded on a scale from 0 to 5. Epithelial COX‐2 index was calculated by multiplying the percentage of positive cells by grade of epithelial COX‐2 intensity. Ischaemic epithelial loss, evident in all implants, recovered rapidly in autografts, and bronchi remained patent. Epithelial loss in non‐treated allografts preceded fibroblast proliferation, resulting in total luminal obliteration. In CsA‐, MP‐, and Aza‐treated allografts epithelial destruction and luminal obliteration were delayed, and these were prevented in CsA‐, MP‐, and everolimus‐treated allografts. COX‐2 expression due to operative ischaemia was evident in all implants on day 2. Thereafter, the epithelial COX‐2 index preceded epithelial injury and obliteration. During the inflammatory response and fibroblast proliferation, COX‐2 expression occurred in macrophages and fibroblasts. In conclusion, in the early stage of OB development, COX‐2 induction occurred in airway epithelial cells prior to luminal obliteration. In addition, the observation that COX‐2 expression in macrophages and fibroblasts paralleled the onset of inflammation and fibroblast proliferation indicates a role in OB development, but the causal relationships need further study. Copyright © 2004 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Toward the gene catalogue of sea urchin development: the construction and analysis of an unfertilized egg cDNA library highly normalized by oligonucleotide fingerprinting.

We describe the use of oligonucleotide fingerprinting for the generation of a normalized cDNA library from unfertilized sea urchin eggs and report the preliminary analysis of this library, which resulted in the establishment of a partial gene catalogue of the sea urchin egg. In an analysis of 21,925 cDNA clones by hybridization with 217 oligonucleotide probes, we were able to identify 6291 clusters corresponding to different transcripts, ranging in size from 1 to 265 clones. This corresponds to an average 3.5-fold normalization of the starting library. The normalized library represents about one-third of all genes expressed in the sea urchin egg. To generate sequence information for the transcripts represented by the clusters, representative clones selected from 711 clusters were sequenced. The construction and preliminary analysis of the normalized library are the first steps in the assembly of an increasingly complete collection of maternal genes expressed in the sea urchin egg, which will provide a number of insights into the early development of this well-characterized model organism.
Mathematics Learning Disabilities

U.S. education suffers from shortcomings that put even children possessing adequate intellectual abilities at risk for low mathematics achievement. Consequently, identifying and understanding children whose academic failure is influenced by a genuine learning disability requires a complex “developmental” research agenda. This perspective suggests the use of sensitive research methods—clinical interviews, ethnographies—to examine the development of children's construction of knowledge in the context of schooling. Researchers should consider such factors as the adequacy of classroom instruction, the availability in children of informal knowledge, the role of motivation, the effects of specific interventions, the role and operation of different cognitive processes in constructing mathematical understanding, children's difficulties across different areas of mathematics, and the development of children's thinking throughout the school years.
Effect of diet on the clearance of estradiol-17 beta in the ewe.

The twinning rate of ewes is poorly related to plasma concentrations of gonadotropins. In this study, we tested an alternative hypothesis for the control of twinning rate, by testing whether nutritional treatment sufficient to affect twinning could alter estrogen metabolism, with a particular focus on the enterohepatic recirculation. Groups of 5 ovariectomized ewes were fed either above maintenance (supplemented) or below maintenance (restricted). The metabolism of estradiol-17 beta was examined by following the fate of a single i.v. injection of 1.45 micrograms [3H]estradiol-17 beta. In both groups, 74% of the radioactivity was recovered from the feces within 10 days, predominantly as free estradiol-17 alpha, but excretion was slower in the nutritionally restricted ewes. A further 6% of injected radioactivity was excreted in the urine, mostly within 24 h, with no effect of dietary group. Radioactivity in plasma was characterized by ion-exchange chromatography and HPLC. Within 30 min of injection, the main circulating radioactive compound was estradiol-17 alpha sulfate. This remained at a greater concentration than free steroid for the next 48 h, and was greater after 16 h (p < 0.05) in plasma of nutritionally restricted ewes than in the supplemented group. At 0.5 and 2 h, the free steroid was almost entirely estradiol-17 beta, but a polar compound, which appeared by 4 h and probably arose by recirculation from the intestine, remained the major unconjugated metabolite in plasma for the next 24 h. Plasma concentrations of this compound were higher (p < 0.05) in the restricted ewes than in the supplemented ewes during this period. (ABSTRACT TRUNCATED AT 250 WORDS)
Isolation and characterization of canine satellite cells

SummarySatellite cells were isolated from biopsies of the biceps femoris of adult dogs. Virtually all cells expressed muscle-specific proteins. Proliferation of satellite cells increased as the concentration of fetal calf serum (FCS) was increased from 1 to 10% of the basal medium. The addition of mitogenic growth factors resulted in greater proliferation than that of cells cultured in basal medium alone. Maximum proliferation was obtained when fibroblast growth factor-basic (FGF2) was added to the medium, but differences existed between sources or types. Proliferation did not plateau when the concentration of recombinant human FGF2 was 75 ng/ml but reached maximum levels when 50 ng/ml of bovine FGF2 or 10 ng/ml of growth hormone or insulin-like growth factor-1 were added to the medium. Proliferation of satellite cells decreased when more than 5 ng/ml of transforming growth factor-α was included in the medium. Exposure of canine satellite cells to chemically defined media induced greater fusion of total nuclei (ODM—34%; 4F, ITT-CF, and SFG—23%) than exposure to other treatments, such as basal medium plus 2 mg/ml of 1-β-d-arabinofuranosylcytosine, 5% chick embryo extract, 1% horse serum (average 9% fused nuclei), or 1% FCS (2% fused nuclei). Actin, myosin, desmin, neural cell adhesion molecule, MyoD1, and myogenin were expressed by canine satellite cells, but expression of major histocompatibility complex class II antigen was not detected. Reverse transcriptase-polymerase chain reaction detected expression of messenger ribonucleic acid for interleukin-6 (IL-6), IL-15, and leukemia inhibitory factor by canine satellite cells. Collectively, these data suggest that isolated canine satellite cells display properties of other types of myogenic cells and may be useful for further study of the regulation of postnatal myogenesis.
Predictability of clinical adverse reactions of drugs by general pharmacology studies.

The Guidelines for General Pharmacology Studies issued by the Japanese Ministry of Health and Welfare (MHW Guideline for short hereafter) is the only one which describes the guidelines for safety pharmacology in details in the world. While the principle pharmacology focuses on the therapeutic effects by studying effects of drugs on the intended or targeted tissues and/or organs, the general pharmacology aims to define the general pharmacological profile of drugs by systematically testing effects on the central nervous system, respiratory and cardiovascular systems, digestive system and other functions of major tissues and organs. Objectives of the general pharmacology studies are to identify the general profile of systemic pharmacological effects of a candidate drug for medical use and to provide information useful for predicting potential