Miracle-dz/UniFAR-FTUs huggingface dataset:
The Meaning of 'choice and control' for People with Intellectual Disabilities who are Planning their Social Care and Support.

BACKGROUND This paper questions consumerist assumptions in current English social care policy and aims to look behind the processes of personalization to interrogate what 'choice and control' means in the lives of a diverse group of people with intellectual disabilities. METHODS Data were from multiple interviews and direct practice recordings with nine people using personal budgets and were analysed using an interpretative approach. RESULTS Identity, other people and personal budget processes were all important for choice and control. People needed to build confidence in themselves as decision-makers, both through peer support and through joint decisions with trusted others. CONCLUSIONS Practitioners need to take into account the spectrum of ways in which people may make decisions. Action needs to be taken both at the micro level of support interactions and at the macro level, with a clearer articulation of independent living in policy and strategy for people with intellectual disabilities.
Instantaneous Orthostatic Hypotension in Children and Adolescents: A New Entity of Orthostatic Intolerance

We are the first to report clinical characteristics and circulatory and catecholamine responses to postural change in 44 children with instantaneous orthostatic hypotension (INOH). The symptoms include chronic fatigue, orthostatic dizziness, weakness, sleep disturbance, syncope or near syncope, headache, and loss of appetite. We divided the patients into two groups: group I (30 patients) had either a recovery time for mean arterial pressure of >25 s or a recovery time of >20 s with a 60% or greater decrease in mean arterial pressure at the initial decrease; group II (14 patients) had a prolonged reduction in systolic arterial pressure of >15% during the later stage of standing (3–7 min) in addition to the criteria for group I. INOH was characterized by a marked reduction in blood pressure at the initial decrease (mean, −55/−27 mm Hg systolic/diastolic). Delayed recovery time of >60 s was found in 21 of 44 patients and orthostatic tachycardia (>35 beats per minute) in 20 of 44. Plasma noradrenaline responses were significantly lower in group I and II than in controls at 1 min of standing and were lower in group II at 5 min of standing. These results suggest that mechanisms responsible for INOH may depend on insufficient sympathetic activation during standing, possibly due to centrally mediated sympathetic inhibition, thus causing impairment of quality of life including school absenteeism. INOH is an important pathologic condition in children with complaints of orthostatic intolerance and can be an unrecognized cause of chronic fatigue. This condition can be identified by using a noninvasive beat-to-beat continuous blood pressure monitoring system.
Structure and Function of the Glutamine Phosphoribosylpyrophosphate Amidotransferase Glutamine Site and Communication with the Phosphoribosylpyrophosphate Site*

Glutamine phosphoribosylpyrophosphate (PRPP) amidotransferase from Escherichia coli exhibits a basal PRPP-independent glutaminase activity having a kcat/Km that is 0.3% of fully active enzyme. Binding of PRPP activates the enzyme by a structural change that lowers the Km for glutamine 100-fold and couples glutamine hydrolysis to synthesis of 5-phosphoribosylamine. By analysis of the x-ray structure of the glutamine site containing bound 6-diazo-5-oxonorleucine, a glutamine affinity analog, and by site-directed mutagenesis we have identified residues important for glutamine binding, catalysis, and coupling with PRPP. Tyr74 is a key residue in the coupling between the sites for glutamine in the NH2-terminal domain and PRPP in the COOH-terminal domain. Arg73 and Asp127 have roles in glutamine binding. The x-ray structure indicates that there are no amino acid side chains sufficiently close to Cys1 to participate as a proton acceptor in formation of the thiolate needed for nucleophilic attack on the carboxamide of glutamine, nor as a general acid for amide nitrogen transfer. Based on the x-ray model of the glutamine site and analysis of a mutant enzyme we propose that the free NH2 terminus of Cys1 functions as the proton acceptor and donor. The results indicate that the side chain of Asn101 and the backbone nitrogen of Gly102 function to stabilize a tetrahedral oxyanion resulting from attack of Cys1 on the glutamine carboxamide. Cys1, Arg73, Asn101, Gly102, and Asp127 are conserved in the NH2-terminal domain of a subfamily of amidotransferases that includes asparagine synthetase, glucosamine 6-phosphate synthase, and glutamate synthase, implying a common function in the four enzymes. Tyr74, on the other hand, is conserved only in glutamine PRPP amidotransferase sequences consistent with a specific role in interdomain coupling. The catalytic framework of key glutamine site residues supports the assignment of glutamine PRPP amidotransferase to a recently described Ntn (NH2-terminal nucleophile) hydrolase family of enzymes.
The Effect of Stance Width on the Electromyographical Activity of Eight Superficial Thigh Muscles During Back Squat With Different Bar Loads

Paoli, A, Marcolin, G, and Petrone, N. The effect of stance width on the electromyographical activity of eight superficial thigh muscles during back squat with different bar loads. J Strength Cond Res 23(1): 246-250, 2009-Many strength trainers believe that varying the stance width during the back squat can target specific muscles of the thigh. The aim of the present work was to test this theory measuring the activation of 8 thigh muscles while performing back squats at 3 stance widths and with 3 different bar loads. Six experienced lifters performed 3 sets of 10 repetitions of squats, each one with a different stance width, using 3 resistances: no load, 30% of 1-repetition maximum (1RM), and 70% 1RM. Sets were separated by 6 minutes of rest. Electromyographic (EMG) surface electrodes were placed on the vastus medialis, vastus lateralis, rectus femoris, semitendinosus, biceps femoris, gluteus maximus, gluteus medium, and adductor maior. Analysis of variance and Scheffè post hoc tests indicated a significant difference in EMG activity only for the gluteus maximus; in particular, there was a higher electrical activity of this muscle when back squats were performed at the maximum stance widths at 0 and 70% 1RM. There were no significant differences concerning the EMG activity of the other analyzed muscles. These findings suggest that a large width is necessary for a greater activation of the gluteus maximus during back squats.
Neuropsychological deficits in temporal lobe epilepsy: A comprehensive review

Temporal lobe epilepsy (TLE) is the most prevalent form of complex partial seizures with temporal lobe origin of electrical abnormality. Studies have shown that recurrent seizures affect all aspects of cognitive functioning, including memory, language, praxis, executive functions, and social judgment, among several others. In this article, we will review these cognitive impairments along with their neuropathological correlates in a comprehensive manner. We will see that neuropsychological deficits are prevalent in TLE. Much of the effort has been laid on memory due to the notion that temporal lobe brain structures involved in TLE play a central role in consolidating information into memory. It seems that damage to the mesial structure of the temporal lobe, particularly the amygdale and hippocampus, has the main role in these memory difficulties and the neurobiological plausibility of the role of the temporal lobe in different aspects of memory. Here, we will cover the sub-domains of working memory and episodic memory deficits. This is we will further proceed to evaluate the evidences of executive function deficits in TLE and will see that set-shifting among other EFs is specifically affected in TLE as is social cognition. Finally, critical components of language related deficits are also found in the form of word-finding difficulties. To conclude, TLE affects several of cognitive function domains, but the etiopathogenesis of all these dysfunctions remain elusive. Further well-designed studies are needed for a better understanding of these disorders.
p38 MAPK Down-regulates Fibulin 3 Expression through Methylation of Gene Regulatory Sequences

Background: p38α MAPK regulates migration/invasion. Results: p38α induces hypermethylation of Fibulin 3 gene regulatory sequences leading to Fibulin 3 down-regulation. This contributes to regulate migration and invasion in MEFs and HCT116 cells. Conclusion: p38α down-regulates fibulin 3 expression through promoter methylation to control p38α-mediated migration and invasion. Significance: To understand the function of new p38α targets in migration/invasion and tumorigenesis. p38 MAPKs regulate migration and invasion. However, the mechanisms involved are only partially known. We had previously identified fibulin 3, which plays a role in migration, invasion, and tumorigenesis, as a gene regulated by p38α. We have characterized in detail how p38 MAPK regulates fibulin 3 expression and its role. We describe here for the first time that p38α, p38γ, and p38δ down-regulate fibulin 3 expression. p38α has a stronger effect, and it does so through hypermethylation of CpG sites in the regulatory sequences of the gene. This would be mediated by the DNA methylase, DNMT3A, which is down-regulated in cells lacking p38α, but once re-introduced represses Fibulin 3 expression. p38α through HuR stabilizes dnmt3a mRNA leading to an increase in DNMT3A protein levels. Moreover, by knocking-down fibulin 3, we have found that Fibulin 3 inhibits migration and invasion in MEFs by mechanisms involving p38α/β inhibition. Hence, p38α pro-migratory/invasive effect might be, at least in part, mediated by fibulin 3 down-regulation in MEFs. In contrast, in HCT116 cells, Fibulin 3 promotes migration and invasion through a mechanism dependent on p38α and/or p38β activation. Furthermore, Fibulin 3 promotes in vitro and in vivo tumor growth of HCT116 cells through a mechanism dependent on p38α, which surprisingly acts as a potent inducer of tumor growth. At the same time, p38α limits fibulin 3 expression, which might represent a negative feed-back loop.
A Domestic cat X Chromosome Linkage Map and the Sex-Linked orange Locus: Mapping of orange, Multiple Origins and Epistasis Over nonagouti

A comprehensive genetic linkage map of the domestic cat X chromosome was generated with the goal of localizing the genomic position of the classic X-linked orange (O) locus. Microsatellite markers with an average spacing of 3 Mb were selected from sequence traces of the cat 1.9× whole genome sequence (WGS), including the pseudoautosomal region 1 (PAR1). Extreme variation in recombination rates (centimorgans per megabase) was observed along the X chromosome, ranging from a virtual absence of recombination events in a region estimated to be >30 Mb to recombination frequencies of 15.7 cM/Mb in a segment estimated to be <0.3 Mb. This detailed linkage map was applied to position the X-linked orange gene, placing this locus on the q arm of the X chromosome, as opposed to a previously reported location on the p arm. Fine mapping placed the locus between markers at positions 106 and 116.8 Mb in the current 1.9×-coverage sequence assembly of the cat genome. Haplotype analysis revealed potential recombination events that could reduce the size of the candidate region to 3.5 Mb and suggested multiple origins for the orange phenotype in the domestic cat. Furthermore, epistasis of orange over nonagouti was demonstrated at the genetic level.
The Causal Relationship between Inflation and Economic Growth inNigeria

In this paper, analysed that Nigeria is the poor country and facing the problem of inflation from last few years. The prime objective of this paper is to analysis the impact on all the developing and under developing countries. We have applied the regression analysis and taken the tile series data. Our results are showing that there negative relationship between Nigeria stock exchange and rate of inflation from last few years. We are also trying to expose that importance of stock exchange in all over the country and due to high inflation rate there is very worst impact on the progress of the economy. Our study suggested that government should make inflation control policies for the better performance.
Snm1-Deficient Mice Exhibit Accelerated Tumorigenesis and Susceptibility to Infection

ABSTRACT The eukaryotic SNM1 gene family has been implicated in a number of cellular pathways, including repair of DNA interstrand cross-links, involvement in VDJ recombination, repair of DNA double-strand breaks, and participation in cell cycle checkpoint pathways. In particular, mammalian SNM1 has been shown to be required in a mitotic checkpoint that causes arrest of cells in prophase prior to chromosome condensation in response to spindle poisons. Here, we report on the phenotype of a knockout of Snm1 in the mouse. Snm1− / − mice are viable and fertile but exhibit a complex phenotype. Both homozygous and heterozygous mice show a decline in survival compared to wild-type littermates. In homozygous mutant males, this reduction in survival is principally due to bacterial infections in the preputial and mandibular glands and to a lesser extent to tumorigenesis, while in homozygous and heterozygous females, it is due almost solely to tumorigenesis. The high incidence of bacterial infections in the homozygous mutant males suggests an immune dysfunction; however, examinations of T- and B-cell development and immunoglobulin class switching did not reveal a defect in these pathways. Crossing of Snm1 mutant mice with a Trp53 null mutant resulted in an increase in mortality and a restriction of the tumor type to lymphomas, particularly those of the thymus. Taken together, these findings demonstrate that Snm1 is a tumor suppressor in mice that in addition has a role in immunity.
Healthy obesity

Purpose of reviewTo introduce the healthy obese phenotype, characterized by favorable cardiometabolic risk factors despite excess adipose tissue. The epidemiology of the healthy obese phenotype is presented, including associated risk of cardiovascular disease (CVD), and potential biologic mechanisms which may give rise to the phenotype are discussed. Recent findingsAlthough it appears that approximately 30% of obese individuals maintain healthy cardiometabolic profiles, little published data exist examining the healthy obese phenotype. The healthy obese do not appear to be at increased risk of incident CVD events compared with at-risk obese, and the location of adipose tissue and the metabolic characteristics of the fat in a given location, including the presence of ectopic fat and associated adipocytokine response, may give rise to the phenotype. Recent data also suggest that weight loss among healthy obese may adversely impact their favorable cardiometabolic profile. SummaryA high prevalence of the healthy obese phenotype has been reported, and these individuals appear to be at no increased risk of CVD. Further research is needed into the mechanisms that allow these individuals to maintain low risk of CVD despite excess adiposity and appropriate weight loss recommendations for this group.
Sepsis up-regulates the expression of connexin 40 in rat aortic endothelium*

Objective:A distinctive feature of sepsis is a pleiotropic modification of membrane protein expression in the vascular endothelium, associated with diminished endothelium-dependent relaxation (endothelial dysfunction). In cultured endothelial cells, inflammatory stimuli alter expression of connexins (Cx), proteins that make up the gap junctions responsible for intercellular communication. In the present study, we tested whether the polymicrobial sepsis induced by cecal ligation and perforation in the rat alters the expression of the connexins present in the vascular endothelium (i.e., Cx37, Cx40, and Cx43). We also examined a possible association between such changes and endothelial dysfunction in this model. Design:Animal study, with two parallel groups. Setting:Animal research facility. Subjects:One hundred four male adult Wistar rats. Interventions:Rats underwent either cecal ligation and perforation to induce sepsis or a sham operation and were killed after a variable time, mostly 24 hrs. Measurements and Main Results:Experiments designed to test for the impact of sepsis on connexin expression disclosed a three-fold increase in Cx40 messenger RNA and protein in the aorta, an effect that peaked at 24 hrs after cecal ligation and perforation, was specific to this connexin (i.e., levels of Cx37 and Cx43 did not vary), and was restricted to the aortic endothelium. Experiments designed to test the permeability of interendothelial gap junctions using the scrape-loading method did not show a change in function in the septic group. Finally, a time-course study was designed to test for a possible association of enhanced Cx40 expression with endothelial dysfunction. Endothelium-dependent relaxation was diminished in rings of aorta when harvested from septic rats before (6 hrs after surgery) but not at the time when enhanced Cx40 expression occurred (12 and 24 hrs). Conclusion:In this experimental model, recovery from an early transient dysfunction of the aortic endothelium is associated with an enhanced expression of aortic endothelial Cx40.
A model of empathic communication in the medical interview.

OBJECTIVE To formulate an empirically derived model of empathic communication in medical interviews by describing the specific behaviors and patterns of interaction associated with verbal expressions of emotion. DESIGN A descriptive, qualitative study of verbal exchanges using 11 transcripts and 12 videotapes of primary care office visits to a total of 21 physicians. SETTING An urban health maintenence organization (HMO), an urban university-based general medicine clinic, and an urban community hospital general medicine clinic. ANALYTIC METHOD: Individual review of transcripts by each research team member to identify instances of expressed or implied emotional themes and to observe the physicians' responses. Individual ratings were compared in group discussions to achieve consensus about the classifications. Similar consensus-based classification was used for review of videotapes. RESULTS We observed that patients seldom verbalize their emotions directly and spontaneously, tending to offer clues instead. If invited to elaborate, patients may then express the emotional concern directly, and the physician may respond with an accurate and explicit acknowledgment. In most of the interviews, the physicians allowed both clues and direct expressions of affect to pass without acknowledgment, returning instead to the preceding topic, usually the diagnostic exploration of symptoms. With emotional expression so terminated, some patients attempted to raise the topic again, sometimes repeatedly and with escalating intensity. We noted a parallel dynamic for encounters in which patients sought praise. We summarized the full interactional sequence in a simple descriptive model. CONCLUSIONS This empirically derived model of empathic communication has practical implications for clinicians and students who want to improve their communication and relationship skills. Based on our observations, the basic empathic skills seem to be recognizing when emotions may be present but not directly expressed, inviting exploration of these unexpressed feelings, and effectively acknowledging these feelings so the patient feels understood. The frequent lack of acknowledgment by physicians of both direct and indirect expressions of affect poses a threat to the patient-physician relationship and warrants further study.
SUPPORTING ECONOMIC GROWTH WITH THE INNOVATION-ORIENTED ENTREPRENEURSHIP

This article aims to examine whether any causal re lationships exist among different types of entrepreneurial activity and eco nomic growth. The theory and some empirical evidence proved positive outcomes of ntrepreneurial activity, but mixed evidence on the role of entrepreneurship in e conomic growth. For the purposes of empirical testing, a longitudinal analysis was employed for 24 differently developed countries to estimate the relationship be twe n different types of entrepreneurial activity and GDP growth rate, controllin g for the impact of countries’ developmental stage and time. The data were obtaine d from the Global Entrepreneurship Monitor database and complemented with dat a from other international sources. The results confirmed that entrepreneurshi p activity, especially innovation-oriented one, is correlated with economic growth, but this relationship is influenced by the economy’s developmental stage as well as by specific characteristics of certain years included in the analysis. Our results in dicate that governmental interventions cannot be the same for all countries; rather, they have to be adjusted to the specific developmental stage of the national econom y and type of entrepreneurship.
Climate change and pollution speed declines in zebrafish populations

Significance Climate change impacts on wildlife populations are likely to be accentuated by pollution. Small (inbred) populations may be more vulnerable to these effects, but empirical data supporting these hypotheses are lacking. We present the first substantial empirical evidence, to our knowledge, for interactive effects on population viability of elevated temperature (climate); an endocrine disrupting chemical, clotrimazole (pollution); and inbreeding. Using the zebrafish (Danio rerio) as a model, we show these three factors interact to skew population sex ratios toward males and that this interaction can lead to increased risk of extinction. Our results suggest that climate change and pollution impacts are likely to pose significant extinction risks for small, endangered populations exhibiting environmental sex determination and/or differentiation. Endocrine disrupting chemicals (EDCs) are potent environmental contaminants, and their effects on wildlife populations could be exacerbated by climate change, especially in species with environmental sex determination. Endangered species may be particularly at risk because inbreeding depression and stochastic fluctuations in male and female numbers are often observed in the small populations that typify these taxa. Here, we assessed the interactive effects of water temperature and EDC exposure on sexual development and population viability of inbred and outbred zebrafish (Danio rerio). Water temperatures adopted were 28 °C (current ambient mean spawning temperature) and 33 °C (projected for the year 2100). The EDC selected was clotrimazole (at 2 μg/L and 10 μg/L), a widely used antifungal chemical that inhibits a key steroidogenic enzyme [cytochrome P450(CYP19) aromatase] required for estrogen synthesis in vertebrates. Elevated water temperature and clotrimazole exposure independently induced male-skewed sex ratios, and the effects of clotrimazole were greater at the higher temperature. Male sex ratio skews also occurred for the lower clotrimazole exposure concentration at the higher water temperature in inbred fish but not in outbred fish. Population viability analysis showed that population growth rates declined sharply in response to male skews and declines for inbred populations occurred at lower male skews than for outbred populations. These results indicate that elevated temperature associated with climate change can amplify the effects of EDCs and these effects are likely to be most acute in small, inbred populations exhibiting environmental sex determination and/or differentiation.