Miracle-dz/UniFAR-FTUs huggingface dataset:
Self-reported sleep duration and napping, cardiac risk factors and markers of subclinical vascular disease: cross-sectional study in older men

Studyobjectives Daytime sleep has been associated with increased risk of cardiovascular disease and heart failure (HF), but the mechanisms remain unclear. We have investigated the association between daytime and night-time sleep patterns and cardiovascular risk markers in older adults including cardiac markers and subclinical markers of atherosclerosis (arterial stiffness and carotid intima-media thickness (CIMT)). Methods Cross-sectional study of 1722 surviving men aged 71–92 examined in 2010–2012 across 24 British towns from a prospective study initiated in 1978–1980. Participants completed a questionnaire and were invited for a physical examination. Men with a history of heart attack or HF (n=251) were excluded from the analysis. Results Self-reported daytime sleep duration was associated with higher fasting glucose and insulin levels (p=0.02 and p=0.01, respectively) even after adjustment for age, body mass index, physical activity and social class. Compared with those with no daytime sleep, men with daytime sleep >1 hour, defined as excessive daytime sleepiness (EDS), had a higher risk of raised N-terminal pro-brain natriuretic peptide of ≥400 pg/mL, the diagnostic threshold for HF (OR (95% CI)=1.88 (1.15 to 3.1)), higher mean troponin, reduced lung function (forced expiratory volume in 1 s) and elevated von Willebrand factor, a marker of endothelial dysfunction. However, EDS was unrelated to CIMT and arterial stiffness. By contrast, night-time sleep was only associated with HbA1c (short or long sleep) and arterial stiffness (short sleep). Conclusions Daytime sleep duration of >1 hour may be an early indicator of HF.
In vitro measurement of the impact of human milk oligosaccharides on the faecal microbiota of weaned formula‐fed infants compared to a mixture of prebiotic fructooligosaccharides and galactooligosaccharides

Aims: To investigate the impact of human milk oligosaccharides (HMOs) from a single donor (SO), HMOs from multiple donors (PO), a fructooligosaccharides and galactooligosaccharides mixture (FG) on the composition of a batch culture inoculated with faecal microbiota from formula‐fed infants.
Do Customers Value CSR Disclosure? Evidence from Italian Family and Non-Family Firms

CSR reporting is a relevant part of a firm’s dialogue with stakeholders, therefore it is of interest to study whether this form of communication is an effective tool for gaining customers’ support. This paper addresses this issue by comparing the effect of CSR disclosure on family and non-family firms’ revenues. In doing so, we analyze a sample of Italian non-financial listed firms and we control for the effect of visibility to stakeholders, governance characteristics, risk, and several accounting variables. We find that CSR reporting has a significant effect on revenues when a company is characterized by consumer proximity, in terms of product or services visibility for consumers, but that the effect is positive for family firms and negative for non-family companies.
The Safety and Efficacy of a Fentanyl Patient-Controlled Transdermal System for Acute Postoperative Analgesia: A Multicenter, Placebo-Controlled Trial

A noninvasive method of delivery of parenteral opioids for management of acute pain may offer logistic advantages for patients and nursing staff. A patient-controlled transdermal system (PCTS) under development consists of a preprogrammed, self-contained drug-delivery system that uses electrotransport technology (E-TRANS®, ALZA Corp, Mountain View, CA) to deliver 40 &mgr;g of fentanyl HCl over 10 min per on-demand dose for patient-controlled analgesia (PCA). In this randomized, double-blinded, placebo-controlled trial we compared the efficacy and safety of on-demand fentanyl HCl PCTS 40 &mgr;g against placebo for postoperative pain up to 24 h after major abdominal, orthopedic, or thoracic surgery in 205 patients. The primary efficacy measurement was the percentage of patients withdrawn from the study because of inadequate analgesia after completing at least 3 h of treatment. Secondary efficacy measures included mean pain intensity (using visual analog scales), patient global assessments, and investigator global assessments. Of 189 patients considered evaluable for efficacy, 25% of patients in the fentanyl HCl PCTS 40 &mgr;g group withdrew because of inadequate analgesia, compared with 40.4% of the placebo group (P < 0.05). Use of fentanyl HCl PCTS 40 &mgr;g was associated with lower VAS scores and higher mean patient and investigator global assessment scores compared with placebo. No patient experienced clinically relevant respiratory depression. This study showed that a fentanyl HCl PCTS 40 &mgr;g for PCA was superior to placebo and well tolerated for the control of moderate to severe postoperative pain for up to 24 h after major surgery.
Fluorine-labeled dasatinib nanoformulations as targeted molecular imaging probes in a PDGFB-driven murine glioblastoma model.

Dasatinib, a new-generation Src and platelet-derived growth factor receptor (PDGFR) inhibitor, is currently under evaluation in high-grade glioma clinical trials. To achieve optimum physicochemical and/or biologic properties, alternative drug delivery vehicles may be needed. We used a novel fluorinated dasatinib derivative (F-SKI249380), in combination with nanocarrier vehicles and metabolic imaging tools (microPET) to evaluate drug delivery and uptake in a platelet-derived growth factor B (PDGFB)-driven genetically engineered mouse model (GEMM) of high-grade glioma. We assessed dasatinib survival benefit on the basis of measured tumor volumes. Using brain tumor cells derived from PDGFB-driven gliomas, dose-dependent uptake and time-dependent inhibitory effects of F-SKI249380 on biologic activity were investigated and compared with the parent drug. PDGFR receptor status and tumor-specific targeting were non-invasively evaluated in vivo using (18)F-SKI249380 and (18)F-SKI249380-containing micellar and liposomal nanoformulations. A statistically significant survival benefit was found using dasatinib (95 mg/kg) versus saline vehicle (P < .001) in tumor volume-matched GEMM pairs. Competitive binding and treatment assays revealed comparable biologic properties for F-SKI249380 and the parent drug. In vivo, Significantly higher tumor uptake was observed for (18)F-SKI249380-containing micelle formulations [4.9 percentage of the injected dose per gram tissue (%ID/g); P = . 002] compared to control values (1.6%ID/g). Saturation studies using excess cold dasatinib showed marked reduction of tumor uptake values to levels in normal brain (1.5%ID/g), consistent with in vivo binding specificity. Using (18)F-SKI249380-containing micelles as radiotracers to estimate therapeutic dosing requirements, we calculated intratumoral drug concentrations (24-60 nM) that were comparable to in vitro 50% inhibitory concentration values. (18)F-SKI249380 is a PDGFR-selective tracer, which demonstrates improved delivery to PDGFB-driven high-grade gliomas and facilitates treatment planning when coupled with nanoformulations and quantitative PET imaging approaches.
Life beyond the classroom: The transition to retirement by long-serving educators

Using a qualitative, multiple case study research approach, the personal stories of eight K-12 educators who retired within the past six years were gathered and analyzed. The goal of the study was to understand how educators struggle, or do not struggle, with the life changing event of bringing closure to a career after spending decades in the classroom. Upon analysis of the data, three key themes were identified: 1. The individuals had control over the timing of their retirement; all participants knew it was the right time to make the transition out of the classroom. 2. Each person is happy with both the choices they made in the retirement process, and with the life they now lead. 3. While the length of time and degree of involvement differed, each person wanted to remain connected to their school and colleagues once the decision was made to retire. The study revealed some of the struggles and joys the individuals experienced during their transition out of the classroom environment. From increased freedom to choose what to do on the spur of the moment, to being able to help elderly parents struggling with health problems, the participants in this study were busy on a day-to-day basis and had established a new balance and flow to their life.
Elementary accreditation: Pro forma or substance? A view from inside the schoolhouse gates

Since the publication of A Nation at Risk in 1986, educators, government officials and community members have grappled with the unwieldy task of defining effective measures of school improvement. Calls for accountability and improvement resound in the halls of legislatures, the media, and in communities nationwide. The accreditation of schools has served as a conduit for accountability, but has it served as a vehicle for improvement? This study sought to determine how closely the process of elementary accreditation through the New England Association of Schools and Colleges (NEASC) aligns with research-based models of effective school change and acts as a leverage point for school reform. The study focused on determining the impact and value of elementary school accreditation procedures on school improvement initiatives in five elementary schools in the New England States, as reported by school leaders, teachers and support personnel whose schools have participated in the NEASC accreditation process. Integrating quantitative and qualitative methodological approaches, the study employed a survey and interviews to gather responses to questions designed to explore the relationship between NEASC accreditation research-based models of effective school improvement. The impact of participation in NEASC accreditation on school change efforts, professional inquiry, curriculum, instruction and assessment, community support, and student achievement are reported and analyzed with differences noted by role and school. Analysis of the survey data revealed that respondents valued participation in the elementary accreditation process and identified it as an effective means of school improvement. Complementarity of results was noted in the data analysis of the qualitative and quantitative data. Significant differences in responses by role were noted, with school leaders attributing more value to the process than teachers or support personnel. Significant differences were identified between schools and were described using a framework (Timar, 1989) adapted to analyze the mode of implementation utilized by each school to accomplish the accreditation tasks. Recommendations for changes in the accreditation process and suggestions for future research are included in the study.
Impairment of vascular endothelial nitric oxide synthase activity by advanced glycation end products

Endothelial damage is believed to play a key role in the development of both micro‐ and macrovascular disease in diabetes, and advanced glycation end products (AGEs) may contribute importantly to this. To determine whether glucose‐derived AGEs can cause endothelial dysfunction, we examined the effects of albumin AGE‐modified by glucose (AGE‐Glu) both in vivo, after injection into rabbit femoral artery, and in vitro on rabbit aortic rings and cultured human umbilical vein endothelial cells (HUVEC). Exposure of blood vessels to AGE‐Glu, in vivo and in vitro, inhibited endothelium‐dependent vasorelaxation, whereas unmodified albumin did not. In isolated rabbit aorta, this effect was reversible after AGE‐Glu washout, and the response to the endothelium‐independent vasodilator sodium nitroprusside was unaffected by AGE‐Glu. In HUVEC, AGE‐Glu inhibited endothelial nitric oxide synthase activity, and this was associated with a decrease in serine phosphorylation of this enzyme. Longer term (72 h) incubation decreased HUVEC viability. Use of specific antibodies demonstrated that these effects were mediated by Nε‐(carboxymethyl)lysine (CML), an important AGE found in vivo, and by the AGE‐R1 receptor. Furthermore, these effects all occurred at CML concentrations similar to those found in the plasma of diabetic patients. These results suggest an important role of AGE in the pathogenesis of diabetic vasculopathy.
Time Is Brain—Quantified

Background and Purpose— The phrase “time is brain” emphasizes that human nervous tissue is rapidly lost as stroke progresses and emergent evaluation and therapy are required. Recent advances in quantitative neurostereology and stroke neuroimaging permit calculation of just how much brain is lost per unit time in acute ischemic stroke. Methods— Systematic literature-review identified consensus estimates of number of neurons, synapses, and myelinated fibers in the human forebrain; volume of large vessel, supratentorial ischemic stroke; and interval from onset to completion of large vessel, supratentorial ischemic stroke. Results— The typical final volume of large vessel, supratentorial ischemic stroke is 54 mL (varied in sensitivity analysis from 19 to 100 mL). The average duration of nonlacunar stroke evolution is 10 hours (range 6 to 18 hours), and the average number of neurons in the human forebrain is 22 billion. In patients experiencing a typical large vessel acute ischemic stroke, 120 million neurons, 830 billion synapses, and 714 km (447 miles) of myelinated fibers are lost each hour. In each minute, 1.9 million neurons, 14 billion synapses, and 12 km (7.5 miles) of myelinated fibers are destroyed. Compared with the normal rate of neuron loss in brain aging, the ischemic brain ages 3.6 years each hour without treatment. Altering single input variables in sensitivity analyses modestly affected the estimated point values but not order of magnitude. Conclusions— Quantitative estimates of the pace of neural circuitry loss in human ischemic stroke emphasize the time urgency of stroke care. The typical patient loses 1.9 million neurons each minute in which stroke is untreated.
A look into German housing markets: A bubble call?

The steep rise in German house prices in recent years raises the question of whether a speculative bubble has already emerged. Using a modified present-value model, we estimate the size of speculative house price bubbles in the German housing market. We do not find evidence for positive bubble accumulation in recent years, and interpret the current bullish run as reflecting the correction of house prices that have been undervalued for more than 10 years. With house prices close to their fair values as of 2018:Q1, our answer to the question is, ‘Not yet, but it is likely soon’.
Differences Between Children With Dyslexia Who Are and Are Not Gifted in Verbal Reasoning

New findings are presented for children in Grades 1 to 9 who qualified their families for a multigenerational family genetics study of dyslexia (impaired word decoding/spelling) who had either superior verbal reasoning (n = 33 at or above 1 2/3 standard deviation, superior or better range; 19% of these children) or average verbal reasoning (n = 31 below population mean but above −2/3 standard deviation, average range; 18% of these children). Evidence-based rationale and results supporting the tested hypotheses are provided: (a) twice exceptional students with superior verbal reasoning and dyslexia significantly outperformed those with average verbal reasoning and dyslexia on reading, spelling, morphological, and syntactic skills, (b) but not on verbal working memory behavioral markers of genetically based dyslexia related to impaired phonological and orthographic word-form storage and processing, naming orthographic symbols (phonological loop), writing orthographic symbols (orthographic loop), and supervisory attention (focus, switch, sustain, or monitor attention). Superior verbal reasoning may mask dyslexia if only very low achievement is used to identify this disorder of oral word reading and written spelling. Instruction for twice exceptional students who have dyslexia, but are also verbally gifted, should focus not only on oral word reading and written spelling but also on the impaired working memory components within intellectually engaging lesson sets. These findings for gifted students with dyslexia are situated within the broader context of the many kinds of twice exceptionalities related to specific learning disabilities that exist in school-age children and youth.
Variation in chlorobenzoate catabolism by Pseudomonas putida P111 as a consequence of genetic alterations

Pseudomonas putida P111 is able to utilize a broad range of monochlorinated, dichlorinated, and trichlorinated benzoates. The involvement of two separate dioxygenases was noted from data on plasmid profiles and DNA hybridization. The benzoate dioxygenase, which converts 3-chlorobenzoate (3-CB), 4-CB, and benzoate to the corresponding catechols via reduction of a dihydrodiol, was shown to be chromosomally coded. The chlorobenzoate-1,2-dioxygenase that converts ortho-chlorobenzoates to the corresponding catechols without the need of a functional dioldehydrogenase was shown to be encoded on plasmid pPB111 (75 kb). Cured strains were unable to utilize ortho-chlorobenzoates for growth. DNA hybridization data indicated that catabolism of the corresponding chlorocatechols was coded on chromosomal genes. Maintenance of plasmid pPB111 was dependent on the presence of ortho-chlorobenzoates in the growth media. A unique variant of P111 (P111D), able to grow on 3,5-dichlorobenzoate (3,5-DCB), was obtained by continuous subculturing from media containing progressively lower and higher concentrations of 3-CB and 3,5-DCB, respectively. The low frequency of segregants able to grow on 2,5-DCB, 2,3-DCB, and 2,3, 5-trichlorobenzoate was evident by lag periods greater than 200 h. Continued subculture on 3,5-DCB resulted in the formation of new plasmid pPH111 (120 kb), which was homologous to pPB111. A probe from the clc operon, which encodes for the chlorocatechol pathway, hybridized to plasmid pPH111 and to the chromosome of the wild-type strain P111 but not to its plasmid pPB111 nor to the chromosome of strain P111A, which had lost the ability to utilize chlorobenzoates. (ABSTRACT TRUNCATED AT 250 WORDS)
DMBT1 polymorphisms: relationship to malignant glioma tumorigenesis.

The deleted in malignant brain tumors 1 (DMBT1) gene on 10q25-26 is a candidate tumor suppressor gene in malignant gliomas, but its role is controversial, e.g., some DMBT1 homozygous deletions reflect unmasking of constitutional deletion polymorphisms by 10q loss. To clarify the role of DMBT1 in gliomagenesis, we investigated three reported deletion hot spots. Homozygous deletions at DMBT1 repeat 2-4 to 2-7 were found in 10 of 73 gliomas with 10q loss, but all 10 deletions reflected unmasking of constitutional hemizygous deletions. Alleles bearing deletion 2-4/2-7 were not selected significantly for by 10q loss, with retention of only 10 of 16 deleted alleles. No homozygous deletion was detected at locus 74k in the 5' upstream region of DMBT1, and four tightly linked polymorphisms were found around this region; chromosome 10q loss randomly affected alleles with or without the variant sequences around locus 74k. Moreover, no significant selection pressure was detected for the haplotype with both deletion 2-4/2-7 and 5' polymorphisms. There was no segregation of deletion 2-4/2-7 in glioma patients compared with unrelated individuals from reference families but a suggestion of a difference in the distribution of the 5' polymorphisms between the reference individuals and glioma patients. Constitutional polymorphisms at DMBT1 repeat 2-9/2-10 appeared common in patients with both benign brain tumors and gliomas. A homozygote for both the 2-4/2-7 deletion and the 5' polymorphisms had a glioma arise at a typical age and without an apparent family cancer predisposition. These data suggest that DMBT1 polymorphisms are not likely primary targets of 10q loss in malignant gliomas and do not support a major role for DMBT1 in gliomagenesis.
Activation of human neutrophil phospholipase D by three separable mechanisms

Activation of human neutrophils by receptor‐mediated agonists, the Ca2+ ionophore A23187, or the protein kinase C activator phorbol myristate acetate all stimulated phospholipase D activity. This was demonstrated by the increased formation of phosphatidic acid, and in the presence of ethanol, phosphatidylethanol (PEt) accumulation. EGTA completely inhibited A23187‐induced PEt formation, but only one‐half of the fMLP‐induced PEt accumulation. Staurosporin, an inhibitor of protein kinase C, strongly inhibited PMA‐induced PEt formation, but actually stimulated the formation of PEt in response to fMLP by several‐fold. Thus, increased cytosolic Ca2+ and activated protein kinase C can each lead to activation of phospholipase D, but neither is required for receptor‐mediated activation of phospholipase D activity. Wortmannin is an irreversible inhibitor of the oxidative burst, but does not inhibit NADPH oxidase or known components of signal transduction. Wortmannin inhibited activation of phospholipase D in response to fMPL. It did not directly inhibit phospholipase D, as the response to A23187 was unaffected. Wortmannin did not inhibit other fMPL‐stimulated events, such as aggregation or adherence. We conclude that inhibition by wortmannin defines a third pathway to activation of phospholipase D. Further, its effect on phospholipase D correlates with its effect on the respiratory burst. —Reinhold, S. L. ; Prescott, S. M. ; Zimmerman, G. A. ; McIntyre, T. M. Activation of human neutrophil phospholipase D by three separable mechanisms. FASEB J. 4: 208‐214; 1990.
Does a Nephron Deficit in Rats Predispose to Salt-Sensitive Hypertension?

Aim: This study tested the hypothesis that a nephron deficit predisposes rats to salt-sensitive hypertension in adulthood. Methods: Female Wistar-Kyoto rats were fed a low (9%) or a normal (20%) protein diet during pregnancy and lactation. Male, birth-weight-matched offspring were paired. One rat from each pair was perfusion fixed at 4 weeks of age and the other rat at 40 weeks of age. Kidneys were removed and nephron number and total renal filtration surface area (FSA) determined using unbiased stereological techniques. The rats that were allowed to grow to adulthood had tail-cuff systolic blood pressure and body weight determined twice weekly. Between 30 and 40 weeks of age, a normal or a high-salt diet was fed to the rats. Results: The offspring of rats fed the low-protein diet were significantly smaller at birth, and at 4 weeks of age they had a significant reduction in kidney volume, nephron number, and total renal FSA when compared to controls. Tail-cuff systolic blood pressure in the offspring from 4 to 29 weeks of age did not significantly differ between the two groups. Administration of a high-salt diet from 30 to 40 weeks of age led to a significant increase in blood pressure in both dietary treatment groups; however, it was not exacerbated in the rats exposed to the low-protein diet in utero. Conclusions: Maternal protein restriction in rats did not lead to salt-sensitive hypertension. Nephron endowment and FSA did not correlate with blood pressure in adulthood.