Miracle-dz/UniFAR-FTUs huggingface dataset:
Olfaction in the Autism Spectrum

The autism spectrum (AS) is characterised by enhanced perception in vision and audition, described by the enhanced perceptual functioning (EPF) model. This model predicts enhanced low-level (discrimination of psychophysical dimensions), and mid- and high-level (pattern detection and identification) perception. The EPF model is here tested for olfaction by investigating olfactory function in autistic and Asperger participants. Experiment 1 targeted higher-order olfactory processing by assessing olfactory identification in nine Asperger, ten autistic, and eleven typically developed individuals. Experiment 2 focused on low-level olfactory processing; we assessed odour detection thresholds and odour discrimination in five Asperger, five autistic, and five typically developed males. Olfactory identification was impaired in autistic participants relative to control and Asperger participants. Typical performance in low-level olfactory processing suggests that neural mechanisms involved in the perceptual phenotype of AS do not affect structures implicated in olfactory processing. Reduced olfactory identification is limited to autistic participants who displayed speech delay and may be due to a reduced facility to use verbal labels. The apparent absence of enhanced olfactory perception of AS participants distinguishes the olfactory system from the other sensory modalities and might be caused by the absence of an obligatory thalamic relay.
Prevention of Pressure Ulcers in the Intensive Care Unit: A Randomized Trial of 2 Viscoelastic Foam Support Surfaces

Aims and objectives: The aim of this study is to compare whether differences exist between 2 viscoelastic foam support surfaces in the development of new pressure ulcers. Background: There is evidence to support the use of viscoelastic foam over standard hospital foam to reduce pressure. A comparative effectiveness study was done to compare 2 viscoelastic foam support surfaces. Design: A randomized controlled trial was carried out. Method: The study was performed in 2 intensive care units between October 1, 2008, and January 4, 2010. Patients (n = 105) admitted to intensive care unit were randomly assigned to viscoelastic foam 1 (n = 53) or viscoelastic foam 2 support surface (n = 52). Results: In total, 42.8% of all patients developed a new pressure ulcer of stage 1 or worse. By stages, pressure ulcer incidence was 28.6%, 13.3%, and 1.0% for stages 1, 2, and 3, respectively. There was no significant difference in pressure ulcer incidence between the viscoelastic foam 1 and 2 groups (X2 = 0.07, df = 1, P > .05). Conclusions: No difference was found between 2 different viscoelastic foam surfaces in the prevention of pressure ulcers in patients treated in intensive care. Relevance to Clinical Practice: Pressure ulcer incidence in critically ill patients remains high. Nurses must compare current products for effectiveness and develop innovative systems, processes, or devices to deliver best practices.
[Expression of WT1 gene and its prognostic value in patients with acute myeloid leukemia].

OBJECTIVE To investigate the expression of Wilms'tumor 1 (WT1) gene in patients with acute myeloid leukemia (AML), and to explore its application in predicting prognosis of AML in patients with wild or mutated nucleophosmin 1(NPM1) and Fms-like tyrosine kinase 3-internal tandem duplication (FLT3-ITD). METHODS One hundred and sixty-seven newly diagnosed AML patients(exclued M3 type) were enrolled in this study. The survival of patients were analyzed with Kaplan-Meier method. The clinical data, laboratory findings and the survival of patients were analyzed and compared between patients with high WT1 expression (high-WT1 group) and those with low WT1 expression (low-WT1 group), as well as among the patients with NPM1 or FLT3-ITD wild type and mutants. RESULTS The overall response rates (ORR) in high-WT1 and low-WT1 groups were 65.9% (83/126) and 95.1% (39/41), respectively (P<0.01). Compared with the low-WT1 group, the high-WT1 group had lower 2-y overall survival (OS) rate (46.1% vs. 75.2%, P<0.05) and 2-y disease free survival (DFS) rate (43.5% vs. 68.5%, P<0.05). After induction chemotherapy, the patients with decreased WT1 gene expression ≥ 1log was associated with higher ORR and 2-y OS rate (all P<0.05), but the advantage of 2-y DFS rate was not shown (P>0.05). In patients with NPM1 wild type, the high-WT1 group had inferior ORR and 2-y OS rate (all P<0.05), while in the patients with FLT3-ITD wild type, the high-WT1 group had inferior ORR, 2-y OS rate and 2-y DFS rate (all P<0.05). In patients with NPM1 or FLT3 -ITD mutations, the WT1 expression had no significantly predicting values in treatment efficacy and survival (all P>0.05). CONCLUSIONS WT1 gene overexpression indicated poor prognosis of AML patients; the patients with decreased WT1 gene expression ≥ 1 log after the first induction therapy show better prognosis than those with<1 log. The WT1 gene expression level at diagnosis can be used as an unfavorable prognostic factor for AML patients with NPM1 or FLT3-ITD wild types.
In vitro and in vivo characterization of conantokin-R, a selective NMDA receptor antagonist isolated from the venom of the fish-hunting snail Conus radiatus.

The purification, characterization, and synthesis of conantokin-R (Con-R), an N-methyl-D-aspartate (NMDA) receptor peptide antagonist from the venom of Conus radiatus, are described. With the use of well defined animal seizure models, Con-R was found to possess an anticonvulsant profile superior to that of ifenprodil and dizocilpine (MK-801). With voltage-clamp recording of Xenopus oocytes expressing heteromeric NMDA receptors from cloned NR1 and NR2 subunit RNAs, Con-R exhibited the following order of preference for NR2 subunits: NR2B approximately NR2A > NR2C >> NR2D. Con-R was without effect on oocytes expressing the alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) receptor subunit GluR1 or the kainate receptor subunit GluR6. In mouse cortical neurons voltage-clamped at -60 mV, Con-R application produced a slowly developing block of inward currents evoked by 10 microM NMDA and 1 microM glycine (IC(50) = 350 nM). At 3 microM, Con-R did not affect gamma-aminobutyric acid- or kainate-evoked currents. Con-R prevented sound-induced tonic extension seizures in the Frings audiogenic seizure-susceptible mice at i.c. v. doses below toxic levels. It was also effective at nontoxic doses in CF#1 mice against tonic extension seizures induced by threshold (15 mA) and maximal (50 mA) stimulation, and it partially blocked clonic seizures induced by s.c. pentylenetetrazol. In contrast, MK-801 and ifenprodil were effective only at doses approaching (audiogenic seizures) or exceeding (electrical and pentylenetetrazol seizures) those required to produce significant behavioral impairment. These results indicate that the subtype selectivity and other properties of Con-R afford a distinct advantage over the noncompetitive NMDA antagonists MK-801 and ifenprodil. Con-R is a useful new pharmacological agent for differentiation between the anticonvulsant and toxic effects of NMDA antagonists.
Broadly neutralizing antibodies from an individual that naturally cleared multiple hepatitis C virus infections uncover molecular determinants for E2 targeting and vaccine design

Cumulative evidence supports a role for neutralizing antibodies contributing to spontaneous viral clearance during acute hepatitis C virus (HCV) infection. Information on the timing and specificity of the B cell response associated with clearance is crucial to inform vaccine design. From an individual who cleared three sequential HCV infections with genotypes 1b, 1a and 3a strains, respectively, we employed peripheral B cells to isolate and characterize neutralizing human monoclonal antibodies (HMAbs) to HCV after the genotype 1 infections. The majority of isolated antibodies, designated as HMAbs 212, target conformational epitopes on the envelope glycoprotein E2 and bound broadly to genotype 1–6 E1E2 proteins. Further, some of these antibodies showed neutralization potential against cultured genotype 1–6 viruses. Competition studies with defined broadly neutralizing HCV HMAbs to epitopes in distinct clusters, designated antigenic domains B, C, D and E, revealed that the selected HMAbs compete with B, C and D HMAbs, previously isolated from subjects with chronic HCV infections. Epitope mapping studies revealed domain B and C specificity of these HMAbs 212. Sequential serum samples from the studied subject inhibited the binding of HMAbs 212 to autologous E2 and blocked a representative domain D HMAb. The specificity of this antibody response appears similar to that observed during chronic infection, suggesting that the timing and affinity maturation of the antibody response are the critical determinants in successful and repeated viral clearance. While additional studies should be performed for individuals with clearance or persistence of HCV, our results define epitope determinants for antibody E2 targeting with important implications for the development of a B cell vaccine.
Job satisfaction in nursing: validation of a new instrument for the UK.

AIM To develop a new, valid and reliable instrument that has been designed and evaluated to measure job satisfaction as perceived by nurses with specific aspects of contemporary nursing. BACKGROUND Job satisfaction is a key concept within workforce research in nursing and is particularly important within the present climate in the UK due to findings linking satisfaction with both quality of care and retention of nurses. METHOD(S) Exploratory and confirmatory factor analyses were carried out on a large longitudinal dataset from a study of Adult-branch diploma-qualified nurses in England who completed the scale at three time-points after qualification. RESULTS A six-factor solution was supported and replicated in a further sample of recently qualified graduate nurses. The instrument was also acceptably reliable. CONCLUSION This new instrument is a concise, highly practical and flexible tool, which can be used in a range of health care settings and in different measurement contexts.
Comparison of antibody reactivity to human immunodeficiency virus type 1 (HIV-1) gp160 epitopes in sera from HIV-1-infected individuals from Tanzania and from the United States

In this study, we compared sera from 159 human immunodeficiency virus type 1 (HIV-1)-infected individuals from Tanzania and 103 infected individuals from the United States for antibodies reactive with 10 HIV-1 gp160 epitopes defined by synthetic peptides. Our data indicate that the anti-gp160 antibody fine specificity differs between infected individuals from these two geographically diverse populations. For example, 50% of the Tanzanian sera contained antibodies reactive with an immunodominant HIV-1 gp41 epitope defined by peptide 600-611, whereas 91% of the sera from the United States were reactive. Differences in serologic reactivity between HIV-1-infected individuals from Tanzania and the United States were also observed with gp160 epitopes defined by peptides 503-528 and 846-860. Included among the peptides examined were four which corresponded to the V3 region of gp120. The majority of sera from either country contained antibodies reactive with peptide RP142, whose V3 sequence is based upon that of HIV-1 isolate MN. Further characterization of serologic reactivity suggested that sera from Tanzania were more likely to neutralize HIV-1 isolate IIIB or MN in vitro than were sera from the United States. These differences in antibody fine specificity between HIV-1-infected individuals from Tanzania and the United States suggest that regional isolates of HIV-1 may exist.
Changes in DNA Level of Oncogenic Human Papillomaviruses Other Than Types 16 and 18 in Relation to Risk of Cervical Intraepithelial Neoplasia Grades 2 and 3

Background: Epidemiologic data addressing clinical relevance of viral load fluctuation of oncogenic types other than human papillomavirus (HPV) types 16 and 18 are limited. Methods: A type-stratified set of infections by non-HPV16/18 oncogenic types that were detected at ≥2 visits was randomly selected from women who were enrolled in a clinical trial and followed every 6 months for 2 years for detection of HPV and cervical intraepithelial neoplasia grades 2 and 3 (CIN2/3). Type-specific viral load was measured on both first and last HPV-positive cervical swab samples. Results: CIN2/3 was initially confirmed at the last HPV-positive visit for 67 of 439 infections. The increase in risk of CIN2/3 was associated with high, relative to low, viral load at both first and last positive visits [ORadjusted = 3.67; 95% confidence interval (CI), 1.19–11.32] and marginally associated with a change of viral load from low to high levels (ORadjusted = 3.15; 95% CI, 0.96–10.35) for infection by species group alpha-9 non-HPV16 oncogenic types but not species group alpha-5-7 non-HPV18 oncogenic types. Among women with an initial diagnosis of CIN2/3 at the first positive visit, CIN2/3 was more frequently redetected at the last positive visit for infections with, compared with without, high DNA load of species group alpha-9 non-HPV16 oncogenic types at both visits (Pexact = 0.04). Conclusions: In agreement with data on baseline viral load, the viral load change–associated risk of CIN2/3 differs by HPV species groups. Impact: These findings underscore the importance of distinguishing species groups in future studies of clinical relevance of HPV DNA load.
Correlation among cytokines, bronchopulmonary dysplasia and modality of ventilation in preterm newborns: improvement with melatonin treatment

Abstract: Improved survival because of advances in neonatal care has resulted in an increased number of infants at risk for chronic lung disease. Even though the etiology of lung injury is multifactorial, recent animal and clinical data indicate that pulmonary damage depends in large part on the ventilatory strategies used. Ventilator‐associated lung injury was believed to result from the use of high pressure, thus, the term barotraumas. This trauma is believed to involve free‐radical damage. Oxidant injury is a serious cause of lung injury. In the present study, 110 newborns with respiratory distress syndrome were studied; 55 were treated with melatonin and the other 55 with placebo. All the subjects were mechanically ventilated with or without guaranteed volume. Proinflammatory cytokines [interleukin (IL)‐6, IL‐8 and tumor necrosis factor (TNF)‐α] were measured in tracheobronchial aspirate and the clinical outcome was evaluated. Melatonin treatment reduced the proinflammatory cytokines and improved the clinical outcome. The beneficial action of melatonin presumably related to its antioxidative actions.
Re-evaluating the Rose approach: comparative benefits of the population and high-risk preventive strategies

Background Options for the prevention of cardiovascular disease, the greatest global cause of death, include population preventive measures (the Rose approach), or specifically seeking out and managing high-risk cases. However, the likely benefit of a population approach has been recently questioned. Objective To compare the estimated effects of population strategies at varying levels of population-wide risk factor reduction and high-risk strategies at varying rates of screening uptake on cardiovascular disease mortality. Methods Data (of 109 954 participants) were pooled from six European general population cohort studies [the high-risk cohorts from the SCORE (Systematic COronary Risk Evaluation) dataset]. The effects of various population and high-risk strategies for the reduction of risk factors were estimated by calculating the change in 10-year risk of cardiovascular disease mortality (SCORE risk) before and after the particular intervention. Risk factors studied were: total cholesterol, blood pressure and smoking. Results At population level, if a 10-year reduction of blood cholesterol level of 10%, a BP reduction of 10% and a 10% reduction in the prevalence of smoking is considered possible, then 9125 lives per million of the population would be saved over 10 years. In contrast, an approach that treats all high-risk individuals with a polypill containing statin, three half-dose antihypertensives and aspirin, with a 20-80% uptake, would save 1861-7452 lives per million. However, the high-risk estimates are very optimistic, as their achievement would require complete compliance. Conclusion High-risk and population strategies are complementary. These estimates of the benefits of each may be useful to health planners, when combined with their local knowledge. Recently, benefits of population strategies have been underestimated.
D1 dopamine receptor‐mediated induction of zif268 and c‐fos in the dopamine‐depleted striatum: Differential regulation and independence from NMDA receptors

Excitatory amino acid afferents from cerebral cortex and dopamine afferents from the substantia nigra synapse on common projection neurons in the striatum. Activation of D1 dopamine receptors increases immediate early gene expression in the striatum and conductance through the N‐methyl‐d‐aspartate (NMDA) receptor. To examine the contribution of NMDA receptor activation to dopamine receptor‐mediated responses, we determined the effects of intrastriatal administration of NMDA antagonists on immediate early gene expression in the striatum and rotational behavior induced by stimulation of the D1 receptor in rats with unilateral dopamine depletions. Systemic administration of SKF 38393 increased c‐fos and zif268 mRNAs in the striatum and induced contralateral rotation. Intrastriatal infusion of the competitive NMDA receptor antagonist (±)‐3‐(2‐carboxypiperazin‐4‐yl)‐propyl‐1‐phosphonic acid caused a dose‐dependent attenuation of SKF 38393‐induced rotation and partially decreased c‐fos mRNA expression. However, D1‐mediated increases in zif268 mRNA were not affected, except by the highest concentration of antagonist used (10 mM). Another competitive antagonist, 2‐amino‐5‐phosphonovaleric acid, had similar effects. Like the competitive antagonists, intrastriatal infusion of the non‐competitive NMDA antagonist MK‐801 partially decreased c‐fos, but not zif268, mRNA in the area around the microdialysis probe. However, unlike competitive antagonists, local infusion of 1 mM MK‐801 potentiated D1‐mediated increases in c‐fos and zif268 mRNAs in lateral striatum. These data suggest that 1) some D1 dopamine receptor‐mediated effects on striatal function are independent of ongoing NMDA receptor activation, whereas other effects are at least partially mediated by NMDA receptor activity in the striatum, and 2) competitive and non‐competitive antagonists of the NMDA receptor differently affect D1‐mediated immediate early gene expression in the striatum. © 1996 Wiley‐Liss, Inc.
Mode I Interlaminar Fracture of Glass/Epoxy Unidirectional Laminates. Part I: Experimental Studies

The paper presents experimental tests of unidirectional double cantilever beams made of a glass fiber reinforced (GFRP) laminate. The critical value of the strain energy release rate (c-SERR or GIC), i.e., the mode I fracture toughness of the considered material was determined with three different methods: the compliance calibration method (CC), the modified compliance calibration method (MCC), and the corrected beam theory (CBT). Due to the common difficulties in precise definition of delamination initiation force, the Acoustic Emission (AE) technique was applied as an auxiliary source of data. The failure process was monitored, as well, in order to detect and identify different damage phenomena. This was achieved through a detailed analysis of the raw AE signal subjected to fast Fourier transformation (FFT). The frequency spectra revealed three dominating frequency bands with the basic one described by the average value of 63.1 kHz, revealing intensive delamination processes. This way, not only precise values of the critical SERR, but also the information on damage evolution during propagation of delamination, was obtained.
Excitability changes in human cutaneous afferents induced by prolonged repetitive axonal activity.

1. The present study was undertaken to document the excitability changes produced by prolonged high‐frequency trains of impulses in cutaneous afferents of six human subjects. 2. Trains of supramaximal stimuli at 200 Hz for 2 min or less produced a prolonged depression in excitability, consistent with activation of the electrogenic Na+‐K+ pump. Trains of longer duration resulted in an initial period of hyperexcitability which, with 10 min trains, was associated with the sensation of paraesthesiae in all subjects. This transient hyperexcitability gradually gave way to a long‐lasting period of hypoexcitability. 3. The excitability changes were reproducible, and were accompanied by corresponding changes in supernormality, refractoriness, strength‐duration time constant and rheobase current, suggesting that the changes in axonal excitability reflected a change in membrane potential. 4. The transient increase in excitability that follows tetanic trains of 10 min had qualitatively similar effects on cutaneous axons as ischaemia or application of a depolarizing current. The post‐tetanic changes in the supernormal period of sensory axons were those expected from the changes in excitability, without evidence of a gross distortion in its time course, as has been previously demonstrated in a hyperstimulated human motor axon. 5. It is concluded that the post‐tetanic hyperexcitability of human sensory axons is probably driven by increased K+ accumulation in the restricted diffusion space under the myelin sheath, much as in motor axons, the differences in behaviour of sensory and motor axons being explicable by greater inward rectification in sensory axons.
miR-27a-5p Attenuates Hypoxia-induced Rat Cardiomyocyte Injury by Inhibiting Atg7

Acute myocardial infarction (AMI) is an ischemic heart disease with high mortality worldwide. AMI triggers a hypoxic microenvironment and induces extensive myocardial injury, including autophagy and apoptosis. MiRNAs, which are a class of posttranscriptional regulators, have been shown to be involved in the development of ischemic heart diseases. We have previously reported that hypoxia significantly alters the miRNA transcriptome in rat cardiomyoblast cells (H9c2), including miR-27a-5p. In the present study, we further investigated the potential function of miR-27a-5p in the cardiomyocyte response to hypoxia, and showed that miR-27a-5p expression was downregulated in the H9c2 cells at different hypoxia-exposed timepoints and the myocardium of a rat AMI model. Follow-up experiments revealed that miR-27a-5p attenuated hypoxia-induced cardiomyocyte injury by regulating autophagy and apoptosis via Atg7, which partly elucidated the anti-hypoxic injury effects of miR-27a-5p. Taken together, this study shows that miR-27a-5p has a cardioprotective effect on hypoxia-induced H9c2 cell injury, suggesting it may be a novel target for the treatment of hypoxia-related heart diseases.