Miracle-dz/UniFAR-FTUs huggingface dataset:
New Insights into the Mechanism of Methoxyflurane Nephrotoxicity and Implications for Anesthetic Development (Part 1): Identification of the Nephrotoxic Metabolic Pathway

Background: Methoxyflurane nephrotoxicity results from biotransformation; inorganic fluoride is a toxic metabolite. Concern exists about potential renal toxicity from volatile anesthetic defluorination, but many anesthetics increase fluoride concentrations without consequence. Methoxyflurane is metabolized by both dechlorination to methoxydifluoroacetic acid (MDFA, which may degrade to fluoride) and O-demethylation to fluoride and dichloroacetatic acid. The metabolic pathway responsible for methoxyflurane nephrotoxicity has not, however, been identified, which was the aim of this investigation. Methods: Experiments evaluated methoxyflurane metabolite formation and effects of enzyme induction or inhibition on methoxyflurane metabolism and toxicity. Rats pretreated with phenobarbital, barium sulfate, or nothing were anesthetized with methoxyflurane, and renal function and urine methoxyflurane metabolite excretion were assessed. Phenobarbital effects on MDFA metabolism and toxicity in vivo were also assessed. Metabolism of methoxyflurane and MDFA in microsomes from livers of pretreated rats was determined in vitro. Results: Phenobarbital pretreatment increased methoxyflurane nephrotoxicity in vivo (increased diuresis and blood urea nitrogen and decreased urine osmolality) and induced in vitro hepatic microsomal methoxyflurane metabolism to inorganic fluoride (2-fold), dichloroacetatic acid (1.5-fold), and MDFA (5-fold). In contrast, phenobarbital had no influence on MDFA renal effects in vivo or MDFA metabolism in vitro or in vivo. MDFA was neither metabolized to fluoride nor nephrotoxic. Barium sulfate diminished methoxyflurane metabolism and nephrotoxicity in vivo. Conclusions: Fluoride from methoxyflurane anesthesia derives from O-demethylation. Phenobarbital increases in methoxyflurane toxicity do not seem attributable to methoxyflurane dechlorination, MDFA toxicity, or MDFA metabolism to another toxic metabolite, suggesting that nephrotoxicity is attributable to methoxyflurane O-demethylation. Fluoride, one of many metabolites from O-demethylation, may be toxic and/or reflect formation of a different toxic metabolite. These results may have implications for interpreting anesthetic defluorination, volatile anesthetic use, and methods to evaluate anesthetic toxicity.
Biomechanical factors influencing nuclear disruption of the intervertebral disc.

STUDY DESIGN A disc model with full anular division was used to investigate how different biomechanical parameters influence the severity of nuclear disruption during compressive loading. OBJECTIVE To quantify the manner in which flexion, hydration, and loading rate contribute to the breakdown in the intrinsic cohesive structure of the nucleus pulposus. SUMMARY OF BACKGROUND DATA The risk of disc herniation is known to increase when the disc is loaded in flexed positions. However, there is a lack of experimental data showing how a combination of flexion with different loading rates and hydration levels affects the extent of nuclear disruption. METHODS A reproducible state of full hydration was established for isolated bovine caudal discs. A period of static preloading at an applied stress of 1 MPa was used to obtain a consistent state of partial hydration. Then 96 discs were subjected to a full-thickness division of the anulus fibrosus and compressed while hydration level, degree of flexion, and rate of loading were varied systematically. RESULTS A full spectrum of nuclear damage was observed in the tests, ranging from no detectable disruption to sudden sequestration of the entire nucleus. These results were quantified, and a general correlation was established between the severity of disruption and the different loading parameters. CONCLUSIONS The degree of flexion and the level of hydration were shown to play an important role in influencing the tendency of the nucleus to break loose and extrude through a preexisting anular division. Interestingly, the rate of loading appeared to have only a minor effect on the severity of damage induced in discs that incorporated a full depth anular division.
Human Parechovirus Infection in Neonatal Intensive Care

Background: Approximately 5–6% of all infective episodes in neonatal intensive care unit (NICU) are of viral origin. Previous studies suggest that human parechovirus (HPeV) infection presents most commonly in term infants, as a sepsis-like syndrome in which meningoencephalitis is prominent. Our aim was to study the infection rate and associated features of HPeV. Methods: Blood samples were taken from NICU babies older than 48 hours, who were being investigated for late onset sepsis. Clinical and laboratory data were collected at the time of the suspected sepsis episode. Samples were tested using universal primers and probe directed at the 5′-untranslated region of the HPeV genome by reverse transcriptase polymerase chain reaction (RT-PCR). Results were confirmed by electrophoresis and DNA sequencing. Results: HPeV was detected in 11 of 84 samples (13%). These infants had a mean [interquartile range (IQR)] gestational age of 28.9 (26.9–30.6) weeks and mean birth weight of 1.26 (SD = 0.72) kg. The median day of presentation was 16 (IQR: 11–27). These characteristics were similar to the infants without positive viral detection. Six infants presented with respiratory signs. One infant presented with signs of meningitis. Six of the 11 episodes of HPeV infection occurred during the winter months (December to February). No HPeV positive infants had abnormal findings on their 28-day cranial ultrasound examination. Conclusions: We found an HPeV infection rate of 13% in infants being tested for late onset sepsis. HPeV should be considered as a possible cause of sepsis-like symptoms in preterm infants.
The Initiation of Epigenetic Silencing of Active Transposable Elements Is Triggered by RDR6 and 21-22 Nucleotide Small Interfering RNAs1[W][OA]

An active transposable element is originally targeted for DNA methylation and epigenetic silencing. Transposable elements (TEs) are mobile fragments of DNA that are repressed in both plant and animal genomes through the epigenetic inheritance of repressed chromatin and expression states. The epigenetic silencing of TEs in plants is mediated by a process of RNA-directed DNA methylation (RdDM). Two pathways of RdDM have been identified: RNA Polymerase IV (Pol IV)-RdDM, which has been shown to be responsible for the de novo initiation, corrective reestablishment, and epigenetic maintenance of TE and/or transgene silencing; and RNA-dependent RNA Polymerase6 (RDR6)-RdDM, which was recently identified as necessary for maintaining repression for a few TEs. We have further characterized RDR6-RdDM using a genome-wide search to identify TEs that generate RDR6-dependent small interfering RNAs. We have determined that TEs only produce RDR6-dependent small interfering RNAs when transcriptionally active, and we have experimentally identified two TE subfamilies as direct targets of RDR6-RdDM. We used these TEs to test the function of RDR6-RdDM in assays for the de novo initiation, corrective reestablishment, and maintenance of TE silencing. We found that RDR6-RdDM plays no role in maintaining TE silencing. Rather, we found that RDR6 and Pol IV are two independent entry points into RdDM and epigenetic silencing that perform distinct functions in the silencing of TEs: Pol IV-RdDM functions to maintain TE silencing and to initiate silencing in an RNA Polymerase II expression-independent manner, while RDR6-RdDM functions to recognize active Polymerase II-derived TE mRNA transcripts to both trigger and correctively reestablish TE methylation and epigenetic silencing.
Comparison of serum oxidant and antioxidant parameters in familial Mediterranean fever patients (FMF) with attack free period.

OBJECTIVE Familial Mediterranean fever (FMF) is an autoinflammatory, autosomal recessive, inherited disease characterized by recurrent self-limiting attacks of serosal surfaces. The imbalance of oxidants/antioxidants may play a role in such attacks. In this study, we aimed to evaluate the relationship between serum paraoxonase (PON1) activity, PON1 phenotype, and other parameters in patients with FMF and healthy controls. METHODS A total of 120 FMF patients with an attack-free period (AFP) and 65 healthy subjects were included in this study. The serum PON1 activity, stimulated paraoxonase (SPON) activity, PON1 phenotype (representing Q192R polymorphism; QQ, QR, RR), arylesterase activity, total oxidant status (TOS), total antioxidant capacity (TAC), oxidative stress index (OSI), advanced oxidative protein products (AOPP), total thiols (TTL), and ischemia-modified albumin (IMA) and cystatin-c (CYS-C) levels were measured. RESULTS For the QQ phenotype, the median TTL and AOPP levels of the control group were 264.50 (57.75) mol/L and 21.26 (21.17) mmol/L, respectively, whereas the median TTL, AOPP levels of the patients were 309.00 (47.00) mol/L and 12.98 (6.96) mmol/L, respectively. There was a statistically significant difference between the patients and controls with the QQ phenotype in terms of TTL and AOPP (p< 0.001 and p= 0.004, respectively). However, there were no statistically significant differences between the QQ and QR+RR phenotypes with respect to TAC, TOS, OSI, or the other parameters. CONCLUSIONS The FMF patients with AFP had higher TTL and lower AOPP levels than the controls. However, other oxidant and antioxidant parameters were similar among the patients during AFP and the controls.
Order Information in Working Memory: fMRI Evidence for Parietal and Prefrontal Mechanisms

Working memory is thought to include a mechanism that allows for the coding of order information. One question of interest is how order information is coded, and how that code is neurally implemented. Here we report both behavioral and fMRI findings from an experiment that involved comparing two tasks, an item-memory task and an order-memory task. In each case, five letters were presented for storage, followed after a brief interval by a set of probe letters. In the case of the item-memory task, the two letters were identical, and the subject responded to the question, Was this letter one of the items you saw? In the case of the order-memory task, the letters were different, and subjects responded to the question, Are these two letters in the order in which you saw them? Behaviorally, items that were further apart in the sequence elicited faster reaction times and higher accuracy in the Order task. Areas that were significantly more activated in the Order condition included the parietal and prefrontal cortex. Parietal activations overlapped those involved in number processing, leading to the suggestion that the underlying representation of order and numbers may share a common process, coding for magnitude.
Determination of phylloquinone and menaquinones in food. Effect of food matrix on circulating vitamin K concentrations.

Fluctuations in international normalized ratio values are often ascribed to dietary changes in vitamin K intake. Here we present a database with vitamin K(1) and K(2) contents of a wide variety of food items. K(1) was mainly present in green vegetables and plant margarins, K(2) in meat, liver, butter, egg yolk, natto, cheese and curd cheese. To investigate the effect of the food matrix on vitamin K bioavailability, 6 healthy male volunteers consumed either a detergent-solubilized K(1) (3.5 micromol) or a meal consisting 400 g of spinach (3.5 micromol K(1)) and 200 g of natto (3.1 micromol K(2)). The absorption of pure K(1) was faster than that of food-bound K vitamins (serum peak values at 4 h vs. 6 h after ingestion). Moreover, circulating K(2) concentrations after the consumption of natto were about 10 times higher than those of K(1) after eating spinach. It is concluded that the contribution of K(2) vitamins (menaquinones) to the human vitamin K status is presently underestimated, and that their potential interference with oral anticoagulant treatment needs to be investigated.
Size and Development of the Shadow Economy of 31 European and 5 other OECD Countries from 2003 to 2013: A Further Decline

In the Tables 1 to 3 the size and development of 31 European and of five non-European shadow economies over the period 2003-2013 is presented 1 . If we first consider the results of the average size of the shadow economy of the 27 European Union countries, we realize that the shadow economy in the year 2003 was 22.3% (of official GDP), decreased to 19.3% in 2008 and increased to 19.8 % in 2009 and then decreased again to 18.4 % in 2013 2 . If we compare the average of 31 European countries, in 2003 the average size was 22.4%, decreased to 19.4% in 2008, and increased to 19.9% in 2009 and decreased to 18.5 in 2013 (Table 2). If we consider the development of the shadow economy of Australia, Canada, Japan, New Zealand and the USA, we find a similar movement over time (see Table 3.); in 2013 these 5 countries had an average size of the shadow economy of 8.6%, in 2010 this value was 9.7%. If we consider the size of the shadow economies over the last 2 years (2012 and 2013) and compare them with the years 2008/09, we realize that, in most countries, we had again a decrease of the size and development of the shadow economy, which is due to the recovery from the worldwide economic and financial crises. Hence, the most important reason for this decrease is, that, if the official economy is recovering or booming, people have fewer incentives to undertake additional activities in the shadow economy and to earn extra “black” money. The only exceptions are Greece and Spain, where the recession of the official economy is so strong, that it even reduces the demand of the shadow economy activities due to the severe income losses of the Greek and Spanish people; the Greek (Spanish) shadow economy will
Gender dysphoria in adolescence

Abstract Adolescents presenting with gender-related concerns are increasingly seeking support from providers from a variety of disciplines within health care settings across the world. For those treating young people who meet the criteria for the DSM 5 diagnosis of gender dysphoria (GD), complex decisions in clinical care are common. Defining best practice with this population with respect to interventions that span mental health, physical, and surgical domains can be challenging, given a relative dearth of empirical data available; yet practice guidelines have emerged from different professional organizations which can aid with this. For this review paper, a broad literature search was performed to identify relevant studies pertaining to the care of adolescents with GD. In addition, an overview of trends in clinical practice, including shifts in conceptualization of how clinicians and patients define care that is considered affirming when working with this population, is described. This paper explores the characteristics of referral patterns to specialized clinics, provides a brief overview of gender identity development in adolescence, and then describes the phenomenology of known aetiological factors and co-occurring psychiatric issues in adolescents with GD. Additionally, clinical management considerations that detail assessment aims and common treatment interventions across disciplines will be explored.
Mammalian Fibroblasts Lacking Mitochondrial NAD+-dependent Methylenetetrahydrofolate Dehydrogenase-Cyclohydrolase Are Glycine Auxotrophs*

Primary fibroblasts established from embryos of NAD-dependent mitochondrial methylenetetrahydrofolate dehydrogenase-cyclohydrolase (NMDMC) knockout mice were spontaneously immortalized or transformed with SV40 Large T antigen. Mitotracker Red CMXRos staining of the cells indicates the presence of intact mitochondria with a membrane potential. The nmdmc(-/-) cells are auxotrophic for glycine, demonstrating that NMDMC is the only methylenetetrahydrofolate dehydrogenase normally expressed in the mitochondria of these cell lines. Growth of null mutant but not wild type cells on complete medium with dialyzed serum is stimulated about 2-fold by added formate or hypoxanthine. Radiolabeling experiments demonstrated a 3–10 × enhanced incorporation of radioactivity into DNA from formate relative to serine by nmdmc(-/-) cells. The generation of one-carbon units by mitochondria in nmdmc(-/-) cells is completely blocked, and the cytoplasmic folate pathways alone are insufficient for optimal purine synthesis. The results demonstrate a metabolic role for NMDMC in supporting purine biosynthesis. Despite the recognition of these metabolic defects in the mutant cell lines, the phenotype of nmdmc(-/-) embryos that begin to die at E13.5 is not improved when pregnant dams are given a glycine-rich diet or daily injections of sodium formate.
Ultrastructure of schwann and perineural sheaths at the mouse neuromuscular junction

Intramuscular nerve branches are covered by a complex of epithelial sheaths which decrease in thickness and complexity as the nerves branch to reach ultimate termination of neuromuscular junctions. The outermost layer (epineurium) of intramuscular nerves is composed of thin processes of fibrocytes lacking basement lamina and associated with parallel bundles of collagen. Internal to this layer are two or three layers of interdigitating perineural cells covered with basement lamina. The innermost layer is frequently incompletely covered by basement lamina within the perineural sheath. Schwann cells covered with basement lamina enclose myelinated and unmyelinated axons.
Blessing or Curse

Flows of remittances to Pakistan are being increasingly viewed as a relatively attractive source of external finance, which can help to foster development and manage economic shocks. Remittances have become a major source of revenue, surpassing the volume of foreign direct investment (FDI) and official development assistance (ODA) that the country receives. This study focuses primarily on the stability, cyclicality and stabilization impacts of remittances to Pakistan. It is evident that foreign flows exhibit different types of volatility; remittances are found to be a less volatile source of external finance than FDI and ODA; they are also found to be counter-cyclical and stabilizing, thus serving to stabilize the recipient economy in times of economic downturns. ODA appears to be a-cyclical and stabilizing, whereas FDI emerges as pro-cyclical and destabilizing. Furthermore, remittances are insensitive to cyclical fluctuations in the sending countries. We also consider a structural vector autoregressive (SVAR)-based identification in order to examine the responses of financial flows to innovation in receiving and sending economies. We confirm the counter-cyclical mechanism of remittances with respect to Pakistani output. In particular, our results indicate that remittance flows to Pakistan are mainly explained by the economic conditions in the country.
Price Pass-Through, Household Expenditure, and Industrial Structure: The Case of Taiwan

In order to calculate the pass-through effect from international commodity prices to domestic prices in Taiwan and evaluate their impact on household expenditure patterns and the industrial structure, we conducted an empirical study using data for Taiwan. We found that the price pass-through coefficients for food in Taiwan were in between those for advanced countries and developing economies, which is similar to the situation facing Taiwan in terms of its economic development. However, the estimated coefficients for energy-related prices were slightly different, and this may have resulted from the energy-related industries such as petroleum, electricity and water supply being either oligopolistic or monopolistic and the government mostly adopting subsidies when the fluctuations in energy prices were the largest. It was for these reasons that the price pass-through coefficients were higher. International commodity price shocks were found to affect household consumption patterns by means of the pass-through effect. Although the coefficients for energy-related prices were higher, the decrease in the household consumption of these products was slight because of the government’s subsidy policy. The expenditure on leisure, entertainment and education changed significantly owing to the high price elasticity and income elasticity. The pass-through effect will result in a shift in household expenditure patterns. The impact of commodity shocks on the industrial structure was evident especially in primary industries and secondary industries. Due to food and energy commodities being mainly inputs of these primary and secondary industries, they would have changed more if the pass through effect had been higher.
Introduction pionnière du E- learning à l’Université et son rôle dans l’élaboration de nouvelles compétences technologiques : Le cas de l’EBAD

L’EBAD, l’Ecole de Bibliothecaires Archivistes et Documentalistes de l’Universite Cheikh Anta Diop de Dakar a su tres vite anticiper l’opportunite offerte par les TICE en Afrique en proposant, des les annees 2000 ses diplomes en formation a distance (FADIS). Grace a une domestication reussie des TIC dans les differents niveaux de formation en Presentiel, les diplomes sont assez outilles en termes de competences technologiques pour, au besoin, poursuivre leur formation en ligne. Au-dela de ces competences requises, d’autres competences sont personnellement elaborees au fur et a mesure de leur apprentissage a distance. Dans cet article nous nous interrogeons sur l’impact reel des TIC dans la mise a jour des competences des professionnels de l’information issus de la formation a distance de l’EBAD. Nous postulons l’hypothese selon laquelle les apprenants de la formation a distance de l’EBAD, du fait de leur proximite avec leur l’environnement virtuel, developpent plus aisement des strategies d’appropriation des TIC pour une meilleure performance dans leur profession. Nous essayerons d'apporter des elements de reponses a partir d'une analyse comparative des profils de diplomes issus des deux modes de formation.
A fast fractional motion estimation algorithm for high efficiency video coding

Motion estimation (ME) for the high efficiency video coding (HEVC) occupies the largest part in the computational complexity of the HM encoder, which consists of integer ME (iME) and fractional ME (fME). We propose a fast fME algorithm that reduces its complexity substantially by reducing the number of search points to less than a half, based on statistical observations, in which four search points are selected only in the horizontal and vertical directions for half-pel search and three search points that have the smaller absolute value of the motion vector difference are selected from eight candidates for quarter-pel search. The effective number of search points in the proposed fME algorithm is reduced to about 60% and the interpolation filtering is also reduced to about 55%, compared to that of the fME in the HM encoder while experimental results show that its Bjontegaard delta (BD) rate degradation is 0.93% for the five class-B video sequences.
The Post-Keynesian Approach to Economics

This major new book provides a coherent critique of the neo-classical synthesis together with a comprehensive and systematic introduction to the post-Keynesian alternatives. Professor Arestis demonstrates that post-Keynesian economics offers a challenge to conventional neo-classical economics. He argues that although post-Keynesianism is not problem-free, it nevertheless offers a more satisfactory explanation of ‘real’ phenomena.