Miracle-dz/UniFAR-FTUs huggingface dataset:
Increased C-telopeptide Cross-linking of Tendon Type I Collagen in Fibromodulin-deficient Mice*

Background: Collagen cross-linking mechanisms must be regulated to obtain tissue-specific collagen fiber properties. Results: Deficiency in collagen-associated protein fibromodulin leads to excessively cross-linked specific domain of collagen. Conclusion: Fibromodulin modulates site-specific cross-linking of collagen. Significance: This is the first report showing that a collagen-associated protein can modulate cross-linking of specific collagen domains. The controlled assembly of collagen monomers into fibrils, with accompanying intermolecular cross-linking by lysyl oxidase-mediated bonds, is vital to the structural and mechanical integrity of connective tissues. This process is influenced by collagen-associated proteins, including small leucine-rich proteins (SLRPs), but the regulatory mechanisms are not well understood. Deficiency in fibromodulin, an SLRP, causes abnormal collagen fibril ultrastructure and decreased mechanical strength in mouse tendons. In this study, fibromodulin deficiency rendered tendon collagen more resistant to nonproteolytic extraction. The collagen had an increased and altered cross-linking pattern at an early stage of fibril formation. Collagen extracts contained a higher proportion of stably cross-linked α1(I) chains as a result of their C-telopeptide lysines being more completely oxidized to aldehydes. The findings suggest that fibromodulin selectively affects the extent and pattern of lysyl oxidase-mediated collagen cross-linking by sterically hindering access of the enzyme to telopeptides, presumably through binding to the collagen. Such activity implies a broader role for SLRP family members in regulating collagen cross-linking placement and quantity.
RELATIONSHIPS BETWEEN THE MENOPAUSE AND RISK FACTORS FOR ISCHAEMIC HEART DISEASE

Abstract. There are still contradictory opinions as to whether there is an association between menopausal age and ischaemic heart disease or not. There is, however, no doubt about the existence of a number of relationships between menstrual status and different risk factors for ischaemic heart disease. Thus, smoking will give rise to an earlier menopause, while the menopause will give rise to increased serum cholesterol and serum triglyceride levels but seems to influence arterial blood pressure and body weight in the opposite way. The relationships between the menopause and risk factors for ischaemic heart disease are complex, which may be one reason for the contradictory results when relating menopausal age to the incidence of ischaemic heart disease.
Impact of neonatal screening and surveillance for the TP53 R337H mutation on early detection of childhood adrenocortical tumors.

PURPOSE The incidence of pediatric adrenocortical tumors (ACTs) is remarkably high in southern Brazil, where more than 90% of patients carry the germline TP53 mutation R337H. We assessed the impact of early detection of this mutation and of surveillance of carriers. PATIENTS AND METHODS Free newborn screening was offered at all hospitals in the state of Paraná. Parents of positive newborns were tested, and relatives in the carrier line were offered screening. Positive newborns and their relatives age < 15 years were offered surveillance (periodic clinical, laboratory, and ultrasound evaluations). ACTs detected by imaging were surgically resected. RESULTS Of 180,000 newborns offered screening, 171,649 were screened, and 461 (0.27%) were carriers. As of April 2012, ACTs had been diagnosed in 11 of these carriers but in only two neonatally screened noncarriers (P < .001); six patient cases were identified among 228 carrier relatives age < 15 years (total, 19 ACTs). Surveillance participants included 347 (49.6%) of 699 carriers. Tumors were smaller in surveillance participants (P < .001) and more advanced in nonparticipants (four with stage III disease; two deaths). Neonatally screened carriers also had neuroblastoma (n = 1), glioblastoma multiforme (n = 1), choroid plexus carcinoma (n = 2), and Burkitt lymphoma (n = 1). Cancer histories and pedigrees were obtained for 353 families that included 1,704 identified carriers. ACTs were the most frequent cancer among carrier children (n = 48). CONCLUSION These findings establish the prevalence of the TP53 R337H mutation in Paraná state and the penetrance of ACTs among carriers. Importantly, screening and surveillance of heterozygous carriers are effective in detecting ACTs when readily curable.
Confidence Management: On Interpersonal Comparisons in Teams

Organizations differ in the degree to which they differentiate employees by ability. We analyze how the effect of differentiation on employee morale may explain this variation. We characterize sufficient conditions for the manager to refrain from differentiation. She refrains from differentiation when employees are of similar ability, especially if absolute levels are high. Avoiding differentiation boosts the self-image of employees. To limit the negative effects of differentiation, the manager's strategy often relies on the coarsest message set possible. The likelihood that the manager differentiates depends on the presence of synergies between employees and on the convexity of the cost of effort function. Finally, we show that in the absence of commitment no differentiation is chosen too often.
Ex Ante and Ex Post Expectations of Outcome Uncertainty and Baseball Television Viewership

Sporting event attendance is determined by ex ante expectations about the quality of the game, but because changing television channels costs nothing, sporting event viewership is influenced by actual game progression. This implies that demand determinants for televised baseball may change as games progress. This study examined the dynamic relationship between demand for televised baseball games and the uncertainty of outcome hypothesis (UOH). In particular, we analyzed inning-varying coefficients in a television rating regression equation. According to our empirical study, there are large dynamics in TV viewership demand for sports events and the marginal effects of factors on viewership changes significantly as innings progress. The estimation results can be summarized as (1) the UOH was shown to be significant not only statistically but also economically; (2) although ex ante variables were more effective in earlier innings and ex post variables were more effective in later innings, we found that ex ante expectations of outcome uncertainty remain significantly influential in later innings; and (3) after the matchup, the ex ante game quality is the second most significant factor among the examined effects on ratings.
Identification of differentially expressed genes in the growth plate of broiler chickens with thiram-induced tibial dyschondroplasia

Tibial dyschondroplasia (TD) is characterized by expansion of the proximal growth plates of the tibiotarsus that fail to form bone, lack blood vessels, and contain non-viable cells. Thiram (a carbamate pesticide), when fed to young broiler chicks, induces TD with high regularity and precision. We used this experimental model to understand the cause of the defects associated with TD by selecting and identifying the genes differentially expressed in the TD growth plate of broiler chickens. Broiler chicks at 7 days of age were randomly divided into two groups. After fasting overnight, they were fed with regular diet (control) or the same diet containing 100 mg/kg thiram for 96 h to induce TD (thiram-fed). mRNA was purified from the growth plates of control and thiram-fed broilers. Forward and reverse-subtracted cDNA libraries were generated by suppression subtractive hybridization technology. Ten selected genes from cDNA libraries were identified by real-time quantitative polymerase chain reaction. All were differentially expressed in TD growth plates (P<0.05 or P<0.01). The levels of collagen type X (Col X), pro-alpha-1 collagen type I (Col I α1), collagen type IX (Col IX), NADH dehydrogenase (NADH DH), cytochrome C oxidase subunit III (COX III), enolase 1, alpha (ENO1), carbonic anhydrase II (CA2) and heat shock protein 90 (Hsp90) mRNA transcripts were up-regulated, while the expression levels of Matrilin 3 (MATN3) and chondromodulin-I (ChM-I) were down-regulated. Col I and Hsp90 were detected by immunohistochemistry at different stages. Given that these genes are involved in matrix formation, endochondral ossification, developmental regulation, electron transport in the mitochondrial respiratory chain and vascularization, our findings may provide new insights into understanding the pathogenesis of TD.
Young people’s experiences of managing asthma and diabetes at school

Purpose: To examine the experiences and concerns of young people and their parents regarding the management of medication for asthma or diabetes whilst at school. Methods: Face-to-face semi-structured interviews were conducted with 69 young people aged 8–15 years (43 with asthma and 26 with diabetes) and their parents (138 interviews in total) in their own homes. Respondents were recruited through randomly selected general practice surgeries in contrasting areas in South East England. Interviews were audio-recorded, transcribed verbatim and analysed using established qualitative analytical procedures. Results: Young people with asthma and diabetes discussed difficulties regarding access to and use of their medicines at school which may jeopardise optimal condition management. School medicines policies could be a further hindrance. Young people endeavour to find ways to accommodate their medication and condition related needs whilst at school, in an attempt to limit the impact of their condition upon school activities such as sport, school trips and relationships with peers. Parents expressed concern regarding the awareness and levels of support available to their sons/daughters, in particular if a crisis should develop. Discussion: In order to ensure optimal care, there is a need for the development of protocols tailored to the needs of young people with different conditions. These should preferably be devised in partnership between the young person, their parents and the school to ensure that the flexibility and support required for optimal management are offered.
How culture shapes the sexual and reproductive health practices among adolescent girls in Eastern Equatoria South Sudan.

Background: From 2011 to 2014, a programme aimed to improve sexual and reproductive health practices among adolescent girls was implemented by the non-governmental organization BRAC in partnership with the Government of South Sudan and with funding from the World Bank. The distinctive culture and norms in South Sudan offered unique challenges to the implementation of such a programme, which this study sought to explore. Objectives: This study investigated the sexual and reproductive health (SRH) behaviour of women and men in Eastern Equatoria State to identify the social norms and beliefs that affect communities’ perception and behaviour regarding SRH issues. Methods: Data were gathered from seven key informant interviews and nine focus groups of adult women and men and adolescent girls and boys in Torit and Magwi Counties in Eastern Equatoria. Results: The study found a strong cultural preference for girls to demonstrate their fertility by beginning to have children at an early age (13–16 years) and to have many children (8–12). It also found that education on HIV/AIDS had been effective. Conclusions: To be effective in South Sudan, adolescent sexual and reproductive health programmes must take the current social norms and practices into account and learn from the successes of HIV/AIDS education programmes. Keywords: sexual and reproductive health, South Sudan, BRAC, adolescent girls, cultural beliefs and practices
Five azacytidine, a DNA methyltransferase inhibitor, specifically inhibits testicular cord formation and Sertoli cell differentiation in vitro

In mammals, Sry, Sox9, and M33 act as regulators at a chromatin level and promote the maturation of embryonic gonads into testes. Recently, it was shown that transcriptional regulation by DNA methylation plays crucial roles in gene expression during the differentiation and development of various cell types. To determine the involvement of DNA methylation in sex determination of the gonad, we developed and performed organ culture of gonad with the DNA methyltransferase inhibitor 5‐azacytidine to induce global DNA methylation status changes. In vitro treatment with 5‐azacytidine specifically inhibited testicular cord formation in a dose‐dependent manner; however, no appreciable defect was observed in ovarian explants. Inhibition of testicular cord was observed only in gonads from11.5 days post‐coitus embryos. These effects were not observed in 5‐azacytidine‐treated gonads from 12.0 days post‐coitus embryos. To determine the effect of 5‐azacytidine on Sertoli and Leydig cell differentiation in the testis, we performed whole mount in situ hybridization analysis. The Leydig and stromal cell marker genes Lhx9, Mfge8, and 3β‐Hsd were normally induced in 5‐azaytidine‐treated testicular explants. Sertoli cell marker genes, Sox9 and MIS were normally induced, but Col9a3, encoding an extracellular matrix component, was inhibited in 5‐azacytidine‐treated testicular explants. Thus, our data show that DNA methylation is involved in testicular cord formation and Sertoli cell differentiation, acting directly on the gonad at 11.5 days post‐coitus. Mol. Reprod. Dev. 75: 1002–1010, 2007. © 2007 Wiley‐Liss, Inc.
Metabolic syndrome and longitudinal changes in cognitive function: a systematic review and meta-analysis.

BACKGROUND Metabolic syndrome (MetS) is associated with an increased risk of coronary heart diseases and stroke. Results on the association of MetS with dementia and cognitive decline have been inconsistent. OBJECTIVE The aim of this study was to examine the association between MetS and longitudinal changes in cognitive function. METHODS Medline, EMBASE, and Scopus databases were searched from inception to June 2013. Longitudinal cohort studies that reported on the association between MetS and change in cognitive function (over two or more time points), were included. RESULTS Random-effects models were used to assess the pooled effect sizes of longitudinal changes in cognitive function associated with MetS. Thirteen studies were included. The total sample size was 19,522 subjects. Follow up duration ranged from 1 to 16 years. In the total sample, a small association of MetS with cognitive decline was observed (SDM 0.06, 95%CI: -0.001, 0.12; p = 0.05). When age-stratified, a marginal significant association between MetS and cognitive decline was observed in the younger old group (≤70 years; SDM = 0.09, 95%CI: -0.003, 0.19; p = 0.05) but not in the older group (>70 years; SDM = 0.03, 95%CI: -0.05, 0.11; p = 0.48). The meta-regression showed that duration of follow up was not associated with changes in cognitive estimates (β = 0.005; p = 0.30). CONCLUSIONS Age appears to modify the association between MetS and cognitive decline. These results emphasize the importance of age-stratified risk prediction models of dementia in subjects with chronic metabolic disorders.
Patterns of dissimilarities among instrument models in measuring PO2, PCO2, and pH in blood gas laboratories.

STUDY OBJECTIVES To ascertain the degree of dissimilarities among blood gas and pH analyzer models of the same and different manufacturers in measurement of PO2, PCO2, and pH using fluorocarbon containing emulsion (FCE) proficiency testing material. DESIGN Statistically and graphically analyze data from six recent proficiency testing surveys for the 20 more frequently used models of analyzers. SETTING AND PARTICIPANTS Over a 2-year period, approximately 900 participants from blood gas laboratories in the United States analyzed similar ampules from each of 30 lots. MEASUREMENTS AND RESULTS Both graphic and statistical comparisons were used to demonstrate differences between manufacturers. For each of the four major manufacturers, comparisons revealed statistically significant differences not only for PO2, but also for PCO2 and pH. Additionally, comparison models within each of the three manufacturers (those with multiple models and > 15 instruments per model represented) disclosed statistically significant dissimilarities among models for each analyte in 115 of 153 model pairings. Previously reported tonometered blood differences among analyzer models for PO2 are qualitatively similar to the differences found in these same models in this FCE study. Model differences are important in research studies and may be clinically important in deciding abnormality, selecting oxygen therapy, or the treatment of patients with respiratory failure or severe respiratory alkalosis. CONCLUSIONS To minimize the likelihood of misleading clinicians, laboratory directors should consider the degree of dissimilarity among blood gas analyzer models in current use and when changing instrumentation.
The prevalence of peripheral arterial disease in a racially diverse population.

BACKGROUND The purpose of this study was to determine the prevalence of peripheral arterial disease (PAD) in white, African American, and English- and Spanish-speaking Hispanic patients. METHODS We screened patients older than 50 years for PAD at 4 primary care clinics located in the Houston Veterans Affairs Medical Center and the Harris County Hospital District. The disease was diagnosed by an ankle-brachial index of less than 0.9. Patients also completed questionnaires to ascertain symptoms of intermittent claudication, walking difficulty, medical history, and quality of life. RESULTS We enrolled 403 patients (136 whites; 136 African Americans; and 131 Hispanics, 81 of whom were Spanish speaking). The prevalence of PAD was 13.2% among whites, 22.8% among African Americans, and 13.7% among Hispanics (P =.06). African Americans had a significantly higher prevalence of PAD than whites and Hispanics combined (P =.02). Among all patients who were diagnosed as having PAD on the basis of their ankle-brachial index, only 5 (7.5%) had symptoms of intermittent claudication. CONCLUSIONS Peripheral arterial disease is a prevalent illness in the primary care setting. Its prevalence varies by race and is higher in African Americans than in whites and Hispanics. Relative to the prevalence of PAD, the prevalence of intermittent claudication is low. Since measurement of the ankle-brachial index is not part of the routine clinic visit, many patients with PAD are not diagnosed unless they develop symptoms of intermittent claudication. Because of this, it is likely that many patients remain undiagnosed. Efforts are needed to improve PAD detection in the primary care setting.
Very low birth weight newborns do not need repeat screening for congenital hypothyroidism.

OBJECTIVE To determine whether repeat screening for congenital hypothyroidism is necessary in newborns weighing <1500 g (very low birth weight [VLBW]). STUDY DESIGN All VLBW infants born in the province of Québec between October 15, 1993, and October 15, 1994, had a second filter paper sample requested at 6 weeks of age to measure thyrotropin and thyroxine, in addition to these measurements for the routine screening sample. We then conducted a survey of all 4 academic pediatric endocrinology clinics in the province, inquiring about cases of permanent primary congenital hypothyroidism (PPCH) in children born weighing <1500 g or who may have been missed by neonatal screening. RESULTS Two specimens were obtained in 465 VLBW newborns. One case of mild transient hyperthyrotropinemia was identified. The survey identified 4 VLBW newborns with PPCH: 1 girl and 1 boy with dyshormonogenesis, 1 athyreotic girl, and 1 girl with thyroid ectopy. All 4 were detected by their initial filter paper specimens. The survey also identified 1 case of PPCH in a girl who had a normal neonatal screen and normal birth weight. CONCLUSIONS VLBW newborns with PPCH can mount an appropriate thyrotropin response and do not need repeat screening for congenital hypothyroidism.
RUNNING READ: CAREER DEVELOPMENT AND SELF-EEFICACY BELIEF Career Development and Self-Efficacy Belief

This article discusses the application of self-efficacy beliefs on career development. This theory was introduced by Hackett and Betz (1981) and has received many extensive studies. There are many factors that may influence career self-efficacy such as gender, culture, parental, and family backgrounds. The methods of increasing career self-efficacy are also discussed. (Contains 34 references.) (Author) Reproductions supplied by EDRS are the best that can be made from the original document. Career Self-Efficacy 1 RUNNING READ: CAREER DEVELOPMENT AND SELF-EEFICACY BELIEF Career Development and Self-Efficacy Belief Melati Sumari Western Michigan University U.S. DEPARTMENT OF EDUCATION Office of Educational Research and Improvement EDUCATIONAL RESOURCES INFORMATION CENTER (ERIC) O This document has been reproduced as received from the person or organization originating it. O Minor changes have been made to improve reproduction quality. Points of view or opinions stated in this document do not necessarily represent official OERI position or policy. PERMISSION TO REPRODUCE AND DISSEMINATE THIS MATERIAL HAS BEEN GRANTED BY TO THE EDUCATIONAL RESOURCES INFORMATION CENTER (ERIC) 1
Characterization of acyl chain position in unsaturated phosphatidylcholines using differential mobility-mass spectrometry[S]

Glycerophospholipids (GPs) that differ in the relative position of the two fatty acyl chains on the glycerol backbone (i.e., sn-positional isomers) can have distinct physicochemical properties. The unambiguous assignment of acyl chain position to an individual GP represents a significant analytical challenge. Here we describe a workflow where phosphatidylcholines (PCs) are subjected to ESI for characterization by a combination of differential mobility spectrometry and MS (DMS-MS). When infused as a mixture, ions formed from silver adduction of each phospholipid isomer {e.g., [PC (16:0/18:1) + Ag]+ and [PC (18:1/16:0) + Ag]+} are transmitted through the DMS device at discrete compensation voltages. Varying their relative amounts allows facile and unambiguous assignment of the sn-positions of the fatty acyl chains for each isomer. Integration of the well-resolved ion populations provides a rapid method (< 3 min) for relative quantification of these lipid isomers. The DMS-MS results show excellent agreement with established, but time-consuming, enzymatic approaches and also provide superior accuracy to methods that rely on MS alone. The advantages of this DMS-MS method in identification and quantification of GP isomer populations is demonstrated by direct analysis of complex biological extracts without any prior fractionation.
Levetiracetam for seizures in children with brain tumors and other cancers

Children with brain tumors and other cancers can suffer from seizures. Unfortunately, most antiepileptic therapies are metabolized by the hepatic cytochrome P450 (CYP) system. Levetiracetam, a newer anticonvulsant, does not undergo CYP metabolism and does not alter the pharmacokinetics of chemotherapy, antiemetics, and corticosteroids, which are metabolized by the liver. We studied 23 patients with cancer and seizures treated with levetiracetam. Over 95% of patients had fewer seizures, with 65.2% becoming seizure free; only one patient experienced an adverse reaction. Levetiracetam is effective and well tolerated in children with brain tumors and other cancers, who are often on multiple enzyme‐inducing drugs. Pediatr Blood Cancer 2009;52:288–289. © 2008 Wiley‐Liss, Inc.