Miracle-dz/UniFAR-FTUs huggingface dataset:
Age-related changes of neuro-endocrine-immune interactions in healthy humans.

Numerous interactions exist among the nervous, endocrine and immune systems, mediated by neurotransmitters, hormones and cytokines. The function of these systems shows patterns of circadian rhythmicity and a number of age-related changes in the 24-hour hormonal and nonhormonal rhythms have been found in older human beings. The aim of this study was to evaluate the presence of altered integration among the nervous, endocrine and immune systems in older adults. Cortisol, melatonin, thyrotropin-releasing hormone (TRH), thyroid-stimulatinghormone (TSH), free thyroxine (FT4), growth hormone (GH), insulin-like growth factor I (IGF-I) and interleukin 2 (IL-2) serum levels were measured and lymphocyte subpopulation analyses were performed on blood samples collected every four hours for 24 hours from seven healthy young subjects aged 36-58 years (mean age +/- s.e. 45.28 +/- 3.31) and from seven healthy old subjects aged 65-78 years (mean age +/- s.e. 68.57 +/- 1.91). There was a statistically significant difference between the groups in the observed values of CD20 (total B cells, higher in the young subjects, t = 2.48, P = 0.028) and CD25 (activated T cells with expression of the alpha chain of IL-2 receptor, higher in elderly subjects, t = -2.23, P = 0.045); DR+ T cells were also higher in elderly subjects, T=34.0, P=0.01). There was no statistically significant difference in the observed values of CD2(total T lymphocytes), CD4 (helper/inducer T cells), CD8 (suppressor/cytotoxic T cells), CD4/CD8 ratio, CD16 (natural killer cells), HLA-DR (B cells and activated T cells), TcR delta 1 (epitope of the constant domain of delta chain of T-cell receptor 1), cortisol, melatonin, TRH, TSH, FT4" GH, IGF-I, IL-2. In the group of younger subjects a clear circadian rhythm was validated for the time-qualified changes of all the factors studied, with the exception of CD16, FT4 and IL-2. In the group of elderly subjects a clear circadian rhythm was validated for the nyctohemeral changes of CD2 (with a phase delay of three hours), CD8, CD4/CD8 ratio, CD16, CD25 (in opposite phase), cortisol (with a phase delay of one hour), melatonin, TSH (with a phase delay of one hour) and GH (with a phase advance of one hour). The results of the current study show that aging is associated with enhanced responsiveness of the T cell compartment and alterations in temporal architecture of neuro-endocrine-immune system.
THE GOAL SETTING COMPONENTS: A STUDY OF SERBIAN EFL LEARNERS

The goal setting theory came into existence almost three decades ago (Locke & Latham 1990). However, goal setting in Serbian EFL students has not been investigated so far. The aim of this paper is to characterize the act of goal setting of Serbian learners and provide a comparison with the results of other EFL learners. The analysis of the questionnaire based on one presented in Gaumer Erickson, Soukup, Noonan & McGurn (2015), which was completed by 100 students, suggests that B1 students possess better values of the goal setting components than B2 students. Correlations between the components provide a large number of statistically significant results. What the goal setting theory implies is that students who are more successful in goal setting will achieve better results. Nevertheless, such an idea is not confirmed by our results since success in learning does not correlate with any of the goals setting components.
Prevalence of obesity among adult Kuwaitis: a cross-sectional study.

OBJECTIVE The association between obesity and different diseases is well documented, especially with non-insulin dependent diabetes, hypertension and heart disease. To prevent proliferation of these and other obesity-related diseases, and to plan adequate health education programmes for the control of obesity, base-line data are required on the prevalence of this condition. The present study is concerned with this need and its purpose is the determination of the prevalence of obesity among adult Kuwaitis. METHOD A cross-section of 3435 Kuwaiti adults forms the study sample. Corpulence was assessed from body mass index (BMI kg/m2) and the mean BMI (+/- standard deviation) was 28.3 (+/- 5.3). RESULTS According to the WHO BMI criteria, the prevalence of obesity was found to be 70.2% (Grade 1) and 36.4% (Grade 2) with BMI as > 25 and > 30, respectively, and was significantly higher (P < 0.001) among women. Obesity among Kuwaitis was found to be higher than reported elsewhere in the world.
Moral Problems Experienced by Nurses when Caring for Terminally Ill People: a literature review

This article is a review of the literature on the subject of how nurses who provide palliative care are affected by ethical issues. Few publications focus directly on the moral experience of palliative care nurses, so the review was expanded to include the moral problems experienced by nurses in the care of the terminally ill patients. The concepts are first defined, and then the moral attitudes of nurses, the threats to their moral integrity, the moral problems that are perceived by nurses, and the emotional consequences of these moral problems are considered in turn. The results show that the moral behaviour of nurses, which is theoretically grounded in commitment to care and to the patient, appears to be shaped by specific processes that lead to engagement or to mental and behavioural disengagement in morally difficult situations. Nurses often appear to fail to recognize the moral dimensions of the problems they experience and also to lack the skills they need to resolve moral problems adequately. Although the findings show that several elements that are beyond the control of nurses, owing to their lack of autonomy and authority, influence their moral experience, intrinsic factors such as feelings of insecurity and powerlessness have a profound effect on nurses’ perceptions and attitudes in the face of moral problems. The moral problems perceived by these nurses are related to end-of-life issues, communication with patients, the suffering of patients, and the appropriateness of the medical treatment.
Pursuing the Phillips Curve in an African Monarchy: A Swazi Case Study

The purpose of this study is to examine whether we can identify a Phillips curve fit for the Kingdom of Eswatini as a low middle income Sub-Saharan Africa monarchy using data collected between 1991 and 2016. In our approach we rely on the recently introduced nonlinear autoregressive distributive lag (N-ARDL) model to a variety of Phillips curve specifications. For robustness sake, we further employ three filters (one-sided HP, two-sided HP, and Corbae-Oularis filters) to extract the gap variables necessary for empirical analysis. Our findings point to a linear, short-run traditional Phillips curve whereas we find strong support for concave shaped unemployment-gap and output–gap based Phillips curve specifications. Given the specific form of concavity discovered in the Phillips curves, the low inflation rate experienced over the last couple of decades can be attributed to a worsening labour and goods markets. Moreover, our evidence further cautions Swazi policymakers of ‘overheating’ of the economy during economic booms in which stabilization tools are required to implemented in such instances.
MGMT promoter methylation correlates with survival benefit and sensitivity to temozolomide in pediatric glioblastoma

Methylation of the DNA‐repair gene O6‐methylguanine‐DNA methyltransferase (MGMT) causes gene silencing. This epigenetic modification has been associated with a favorable prognosis in adult patients with glioblastoma (GBM) who receive temozolomide and other alkylating agents. We explored MGMT promoter methylation in pediatric GBM and its relationship to survival and temozolomide sensitivity.
'The experience of community mental health case management provided from an acute in-patient psychiatric unit'.

In Australia, case management is the cornerstone of mental health service delivery for seriously ill clients living in the community. In this study, case management was provided from an acute, inpatient psychiatric unit; a model thought to be unique. Findings from this qualitative study explicated the experience of case management from client and case manager (CM) perspectives. They note the nature, purpose, processes and outcomes of case management within that context. Findings were positive, suggesting clients and CM's develop a therapeutic alliance through which interventions are implemented and which result in clients experiencing personal (re) integration and enhanced well-being. These findings are discussed and they suggest an alternative model of service delivery well regarded by both clients and CM's.
Migrant Remittances and Macroeconomic Developments in the Source Countries

Decades of studies on migrant remittances make one think that everything has been already said, but the recent dynamics of remittances challenge the accumulated knowledge. The economic downturn in the remittance-source countries led to a decline in the outflows and a further stagnation while the inflows to these countries sharply increased. The role of the source countries in remittances dynamics needs more attention. This article empirically examines the role of a set of macroeconomic indicators on the outflows of remittances in seven of the top ten source countries of remittances. Particular attention is given to the fluctuations in remittance outflows over the international business cycles and more specifically during the recent global crisis. The constructed model found a significant impact of inflation, unemployment and wages in the source countries on the outflow of remittances, while the economic growth has no significant direct impact.
The use of accurate visual acuity measurements in clinical anti‐cataract formulation trials

A standardized visual acuity technique is presented for use in anti‐cataract drug trials. Ferris Logmar charts were used in repeatability studies of vision, visual acuity and pinhole visual acuity measurements for twenty normal subjects (mean (±SD) age 64 ± 6.3 years). Visual acuity measurements were shown to be the most repeatable and thought to be the most suitable for monitoring cataract progression. Repeated visual acuity measurements were made on 29 cataractous eyes of 15 subjects (mean (±SD) age 67.8 ± 7.2 years). A Logmar score change of 0.1 (one line) was shown to be a statistically significant change. This value can be used in statistical analyses of drug efficacy. The normal data gives a mean Logmar visual acuity of 1.15 (Snellen equivalent 6/5). This indicates the inadequacy of using 6/6 as a norm value for visual acuity, even for older patients. As the possibility of reversal of cataract theoretically exists in the early stages of cortical and capsular cataracts, patients with small amounts of these types of cataract are ideal patients for anti‐cataract formulation trials. The normal visual acuity results indicate that the inclusion criteria for clinical trials can include patients with cataracts with visual acuity as good as 6/6.
Involvement of the Aspergillus nidulans protein kinase C with farnesol tolerance is related to the unfolded protein response

Previously, we demonstrated that the Aspergillus nidulans calC2 mutation in protein kinase C pkcA was able to confer tolerance to farnesol (FOH), an isoprenoid that has been shown to inhibit proliferation and induce apoptosis. Here, we investigate in more detail the role played by A. nidulans pkcA in FOH tolerance. We demonstrate that pkcA overexpression during FOH exposure causes increased cell death. FOH is also able to activate several markers of endoplasmic reticulum (ER) stress and the unfolded protein response (UPR). Our results suggest an intense cross‐talk between PkcA and the UPR during FOH‐induced cell death. Furthermore, the overexpression of pkcA increases both mRNA accumulation and metacaspases activity, and there is a genetic interaction between PkcA and the caspase‐like protein CasA. Mutant analyses imply that MAP kinases are involved in the signal transduction in response to the effects caused by FOH.
A 12-MONTH PROSPECTIVE TRIAL OF INJECT AND EXTEND REGIMEN FOR RANIBIZUMAB TREATMENT OF AGE-RELATED MACULAR DEGENERATION

Purpose: To evaluate the safety and efficacy of a strictly applied inject and extend protocol for ranibizumab treatment of age-related macular degeneration. Methods: This is a prospective, multicenter, nonrandomized trial. Patients underwent standard induction with 3 intravitreal doses of 0.5 mg ranibizumab, each 1 month apart. Following this induction, patients were evaluated and received an injection at each visit. If they did not meet set criteria for signs of exudative disease the interval to the next visit was extended by 2 weeks and if exudative disease was present the interval was shortened by 2 weeks. Results: Vision improved by 1.3 lines (P = 0.008); 26% gained ≥3 lines of vision, 74% lost no lines of vision, and 95% avoided loss of ≥3 lines of vision. Conclusion: This study shows that the Inject and Extend protocol is safe and efficacious for the treatment of age-related macular degeneration. Head-to-head studies are needed to compare directly with other regimens currently in use, as well as economic analysis to investigate the financial implications.
Nicotine metabolism: the impact of CYP2A6 on estimates of additive genetic influence

To conduct a pharmacogenetic investigation of nicotine metabolism in twins. One hundred and thirty nine twin pairs [110 monozygotic (MZ) and 29 dizygotic (DZ)] underwent a 30-min infusion of stable isotope-labelled nicotine and its major metabolite, cotinine, followed by an 8-h in-hospital stay. Blood and urine samples were taken at regular intervals for analysis of nicotine, cotinine and metabolites by gas chromatography–mass spectrometry or liquid chromatography–mass spectrometry and subsequent characterization of pharmacokinetic and metabolism phenotypes. DNA was genotyped to confirm zygosity and for variation in the gene for the primary enzyme involved in nicotine metabolism, CYP2A6 (alleles tested: *1, *1×2, *2, *4, *7, *9 and *12). Univariate biometric analyses quantified genetic and environmental influences on each pharmacokinetic measure in the presence and absence of covariates, including measured CYP2A6 genotype. The best-fitting model identified a substantial amount of variation in the weight-adjusted rate of total clearance of nicotine attributable to additive genetic influences [59.4%, 95% confidence interval (CI)=44.7–70.7]. The majority of variation in the clearance of nicotine via the cotinine pathway was similarly genetically influenced (60.8%, 95% CI=46.9–71.5). Heritability estimates were reduced to 54.2% and 51.8%, respectively, but remained substantial after taking into account the effect of variation in CYP2A6 genotype. These results suggest the involvement of additional genetic factors (e.g. uncharacterized or novel CYP2A6 alleles as well as other genes in the metabolic pathway) that remain to be identified.
Estradiol and Testosterone Concentrations Increase with Fasting in Weaned Pups of the Northern Elephant Seal (Mirounga angustirostris)

Although neonatal development is generally associated with increased levels of circulating testosterone (T) and estradiol (E2), food deprivation may inhibit steroidogenesis. Therefore, these potentially conflicting stimuli were examined in fasting weaned northern elephant seal (Mirounga angustirostris) pups by measuring serum concentrations of T, E2, progesterone (P4), and luteinizing hormone (LH) by either radioimmunoassay (P4, LH) or enzymeimmunoassay (T, E2). Blood samples were obtained from 20 male and 20 female pups at both early (<1 wk postweaning) and late (6–8 wk postweaning) periods during their natural postweaning fast. T in males (early: 2.9 ± 0.4 ng/mL; late: 16 ± 2 ng/mL; P < 0.0001) and E2 in females (early: 42 ± 6 pg/mL; late: 67 ± 5 pg/mL; P < 0.01) increased between the two measurement periods, while P4 (early: 2.5 ± 0.3 ng/mL; late: 2.1 ± 0.3 ng/mL; P > 0.05) did not. LH increased (early: 46 ± 4 pg/mL; late: 65 ± 6 pg/mL; P < 0.05) in males but not in females (early: 69 ± 9 pg/mL; late: 65 ± 6 pg/mL; P > 0.05). Increases in LH and T suggest that LH may stimulate T secretion. Alternatively, relatively low concentrations of LH in both males and females may reflect negative feedback inhibition imposed by elevated T and E2 concentrations. Despite the inherent postweaning fast, concentrations of T and E2 increased, suggesting that they may be critical for the continued development of pups. Therefore, compensatory mechanisms may exist that alleviate the fasting‐induced inhibition of gonadal steroidogenesis during neonatal development in elephant seal pups.
Parenting Styles for the Deaf Children in Disseminating Entrepreneurship

This study aims at examining parenting styles for the deaf children in disseminating entrepreneurship. This research employed case study approach using the semi-structured interview technique from parents of deaf children. The result indicated that parenting styles was dominantly by authoritarian, in term of nurturing the children as well as educating responsibility. In addition, the deaf children were also employed by democratic style in encouraging the interest of them. This study also found that parenting styles in disseminating entrepreneurship were influenced by several factors, such as a limited time allocation to learn business and a talent of the children.
The effect of palmitic acid on lipoprotein cholesterol levels

The present study assessed the effect of high versus low palmitic acid intakes of plasma lipoprotein cholesterol levels and on rates for endogenous synthesis of cholesterol in normal and hypercholesterolemic subjects. On day 21 of each diet treatment, a fasting blood sample was drawn for lipoprotein determination and to provide a measure of the background level of deuterium. A priming dose of deuterium was consumed and a second blood sample obtained 24 hours after the first sample. Isotope ratio mass spectrometry was used to determine the incorporation of deuterium into the newly synthesized cholesterol molecule and fractional synthetic rates were calculated. Four diets were formulated to provide combinations of two levels of 16 : 0 at two levels of 18 : 2n–6. Subjects received each of the four diet treatments for 21 days, followed by washout periods of 21 days. Serum total cholesterol and LDL-cholesterol was not significantly affected by the high level of 16 : 0 when diets also contained a high level of 18 : 2n–6. Fractional synthesis rates of cholesterol observed for each diet treatment did not differ significantly, suggesting no relationship between the endogenous synthesis of cholesterol and dietary 16 : 0 content. The results indicate that 16 : 0 has no effect on serum lipoprotein profiles in the presence of recommended intakes for 18 : 2n–6
Different agonist- and antagonist-induced conformational changes in retinoic acid receptors analyzed by protease mapping

The pleiotropic effects of retinoic acid on cell differentiation and proliferation are mediated by two subfamilies of nuclear receptors, the retinoic acid receptors (RARs) and the retinoid X receptors (RXRs). Recently the synthetic retinoid Ro 41-5253 was identified as a selective RAR alpha antagonist. As demonstrated by gel retardation assays, Ro 41-5253 and two related new RAR alpha antagonists do not influence RAR alpha/RXR alpha heterodimerization and DNA binding. In a limited trypsin digestion assay, complexation of RAR alpha with retinoic acid or several other agonistic retinoids altered the degradation of the receptor such that a 30-kDa proteolytic fragment became resistant to proteolysis. This suggests a ligand-induced conformational change, which may be necessary for the interaction of the DNA-bound RAR alpha/RXR alpha heterodimer with other transcription factors. Our results demonstrate that antagonists compete with agonists for binding to RAR alpha and may induce a different structural alteration, suggested by the tryptic resistance of a shorter 25-kDa protein fragment in the digestion assay. This RAR alpha conformation seems to allow RAR alpha/RXR alpha binding to DNA but not the subsequent transactivation of target genes. Protease mapping with C-terminally truncated receptors revealed that the proposed conformational changes mainly occur in the DE regions of RAR alpha. Complexation of RAR beta, RAR gamma, and RXR alpha, as well as the vitamin D3 receptor, with their natural ligands resulted in a similar resistance of fragments to proteolytic digestion. This could mean that ligand-induced conformational changes are a general feature in the hormonal activation of vitamin D3 and retinoid receptors.
mGluR1/5 subtype‐specific calcium signalling and induction of long‐term potentiation in rat hippocampal oriens/alveus interneurones

Hippocampal inhibitory interneurones demonstrate pathway‐ and synapse‐specific rules of transmission and plasticity, which are key determinants of their role in controlling pyramidal cell excitability. Mechanisms underlying long‐term changes at interneurone excitatory synapses, despite their importance, remain largely unknown. We use two‐photon calcium imaging and whole‐cell recordings to determine the Ca2+ signalling mechanisms linked specifically to group I metabotropic glutamate receptors (mGluR1α and mGluR5) and their role in hebbian long‐term potentiation (LTP) in oriens/alveus (O/A) interneurones. We demonstrate that mGluR1α activation elicits dendritic Ca2+ signals resulting from Ca2+ influx via transient receptor potential (TRP) channels and Ca2+ release from intracellular stores. By contrast, mGluR5 activation produces dendritic Ca2+ transients mediated exclusively by intracellular Ca2+ release. Using Western blot analysis and immunocytochemistry, we show mGluR1α‐specific extracellular signal‐regulated kinase (ERK1/2) activation via Src in CA1 hippocampus and, in particular, in O/A interneurones. Moreover, we find that mGluR1α/TRP Ca2+ signals in interneurone dendrites are dependent on activation of the Src/ERK cascade. Finally, this mGluR1α‐specific Ca2+ signalling controls LTP at interneurone synapses since blocking either TRP channels or Src/ERK and intracellular Ca2+ release prevents LTP induction. Thus, our findings uncover a novel molecular mechanism of interneurone‐specific Ca2+ signalling, critical in regulating synaptic excitability in hippocampal networks.
Prognostic Factors for Post-Recurrence Survival in Patients with Thoracic Esophageal Squamous Cell Carcinoma after Curative Resection

Background/Aims: We investigated factors affecting the post-recurrence prognosis in order to develop adequate therapeutic guidelines for determining the indication for treatment of recurrent esophageal squamous cell carcinoma (ESCC). Methods: Ninety-three thoracic ESCC patients who developed postoperative recurrence after undergoing curative esophagectomy with 3-field lymphadenectomy at our institute and who received treatment for recurrence were enrolled in this study. Results: A univariate analysis showed that distant organ recurrence, the number of recurrent tumors, the longest diameter of the largest recurrent tumor, the sum of all of the longest diameters of the recurrent tumors, invasion into adjacent structures and the speed of growth of the representative recurrent tumors were significantly associated with the post-recurrence prognosis. A multivariate analysis showed that distant organ recurrence, the longest diameter of the largest recurrent tumor, invasion into adjacent structures and the speed of growth of the representative recurrent tumors were significantly associated with the prognosis. The patients whose recurrent tumor(s) did not meet all 4 of these factors showed a better prognosis. In contrast, the prognosis of the patients whose recurrent tumor(s) demonstrated all 4 factors was almost the same as that observed in the patients who did not receive any treatment for recurrence. Conclusions: The evaluation of these 4 factors may potentially be used to determine the indication for treatment for recurrence.