Miracle-dz/UniFAR-FTUs huggingface dataset:
Newborn Screening in Slovenia

Abstract Introduction. Newborn screening in whole Slovenia started in 1979 with screening for phenylketonuria (PKU). Congenital hypothyroidism (CH) was added into the programme in 1981. The aim of this study was to analyse the data of neonatal screening in Slovenia from 1993 to 2012 for PKU, and from 1991 to 2012 for CH. Methods. Blood samples were collected from the heels of newborns between the third and the fifth day after birth. Fluorometric method was used for screening for PKU, CH screening was done by dissociationenhanced lanthanide fluorescent immunoassay (DELFIA). Results. From 1993 to 2012, from 385,831 newborns 57 were identified with PKU. 184 newborns out of 427,396 screened from 1991 to 2012, were confirmed for CH. Incidences of PKU and CH in the periods stated are 1:6769 and 1:2323, respectively. Conclusions. Successful implementation of newborn screening for PKU and CH has helped in preventing serious disabilities of the affected children. Adding screening for new metabolic diseases in the future would be beneficial. Izvleček Uvod. Presejanje novorojencev v Sloveniji se je začelo leta 1979 s presejanjem za fenilketonurijo (PKU). Leta 1981 je bil v program presejanja dodan še kongenitalni hipotireoidizem (CH). Cilj te raziskave je analiza podatkov presejanja novorojencev v Sloveniji v obdobju med letoma 1993 in 2012 za PKU ter med letoma 1991 in 2012 za CH. Metode. Vzorci krvi so bili odvzeti petim novorojencem med tretjim in petim dnem življenja. Pri presejanju za PKU se uporablja fluorometrična metoda, presejanje za CH pa poteka z metodo DELFIA. Rezultati. Od leta 1993 do leta 2012 je bil presejalni test za PKU izveden pri 358.831 novorojencih. Pri 57 otrocih je bil PKU potrjen. Pri 427.396 novorojencih med letoma 1991 in 2012 je bil izveden presejalni test za CH. Pri 184 otrocih je bil CH potrjen. V navedenih obdobjih je bila incidenca PKU 1:6769 in incidenca CH 1:2323. Zaključki. Uspešna implementacija presejanja novorojencev za PKU in CH je imela pomembno vlogo pri preprečevanju resnih zapletov pri obolelih otrocih. Smiselno bi bilo v program presejanja vključiti nove metabolne bolezni.
Competing interests: None declared. Ethical approval: Ethics committee of Côte d’Ivoire’s Ministry of Public Health and the Institutional Review Board of the US Centers for Disease Control and Prevention

Lucien, Bondo Monga, Delphine Chia N’guessan, Déborah N’Guessan-Yao, Jean Louis N’Jampo, Patricia Patindé, Albert Seri Sekou, Odette Tossou, Leo Weakland, Christiane Wondji Gozo. At the US Centers for Disease Control and Prevention, we thank Eliane Dogoré for help with coding; David Fluker, Eleanor McLellan, and Robert Strotman for software support; and Thomas Peterman, Marc Bulterys, Richard Jenkins, RJ Simonds, and Monica Nolan for commenting on earlier versions of the manuscript. We also thank two BMJ reviewers for their useful comments and suggestions. This study was presented in part at the XIIth International Conference on AIDS and STDs in Africa, Ouagadougou, Burkina Faso, December 9-13, 2001 [abstract 10BT2-6]. Contributors: See bmj.com. Funding: The research project was funded by the Centers for Disease Control and Prevention (CDC). All of the authors were employed directly or indirectly by the CDC during the design, collection and analysis of data, and write-up of findings. Competing interests: None declared. Ethical approval: Ethics committee of Côte d’Ivoire’s Ministry of Public Health and the Institutional Review Board of the US Centers for Disease Control and Prevention.
Prediction of Molecular Interaction between Platelet Glycoprotein Ibα and von Willebrand Factor using Molecular Dynamics Simulations.

AIM The molecular mechanism of the unique interaction between platelet membrane glycoprotein Ibα (GPIbα) and von Willebrand Factor (VWF), necessary for platelet adhesion under high shear stress, is yet to be clarified. METHODS The molecular dynamics simulation using NAMD (Nanoscale Molecular Dynamics) package with the CHARMM 22 (Chemistry at Harvard Macromolecular Mechanics) force field were used to predict dynamic structural changes occurring in the binding site of A1 domain of VWF and N terminus domain of GPIbα under water soluble condition. RESULTS The mean distance between the mass center of A1 domain of VWF and GPIbα in the stable form was predicted as 27.3 Å. The potential of mean force between the A1 domain of VWF and GPIbα were calculated in conditions of various distances of the mass center between them. All the calculated values were fitted to the Morse potential energy function curve. The maximum adhesive force between A1 domain of VWF and GPIbα was predicted as 62.3 pN by differentiating the potential of mean force with respect to the molecular distance. CONCLUSIONS The molecular dynamics simulation is useful for predicting the dynamic structure changes of protein bonds involved in platelet adhesion and for predicting the adhesive forces generated between their interactions.
Sodium bicarbonate to prevent increases in serum creatinine after cardiac surgery: A pilot double-blind, randomized controlled trial*

Objective:To test whether perioperative sodium bicarbonate infusion can attenuate postoperative increases in serum creatinine in cardiac surgical patients. Design:Double-blind, randomized controlled trial. Setting:Operating rooms and intensive care unit at a tertiary hospital. Patients:Cohort of 100 cardiac surgical patients at increased risk of postoperative acute renal dysfunction. Intervention:Patients were randomized to either 24 hrs of intravenous infusion of sodium bicarbonate (4 mmol/kg) or sodium chloride (4 mmol/kg). Measurements and Main Results:The primary outcome measure was the proportion of patients developing acute renal dysfunction defined as a postoperative increase in plasma creatinine concentration >25% of baseline within the first five postoperative days. Secondary outcomes included changes in plasma creatinine, plasma urea, urinary neutrophil gelatinase-associated lipocalin, and urinary neutrophil gelatinase-associated lipocalin/urinary creatinine ratio. Patients were well balanced for baseline characteristics. Sodium bicarbonate infusion increased plasma bicarbonate concentration (p < 0.001), base excess (p < 0.001), plasma pH (p < 0.001), and urine pH (p < 0.001). Fewer patients in the sodium bicarbonate group (16 of 50) developed a postoperative increase in serum creatinine compared with control (26 of 50) (odds ratio 0.43 [95% confidence interval 0.19–0.98]), (p = 0.043). The increase in plasma creatinine, plasma urea, urinary neutrophil gelatinase-associated lipocalin, and urinary neutrophil gelatinase-associated lipocalin/urinary creatinine ratio was less in patients receiving sodium bicarbonate, (p = 0.014; p = 0.047; p = 0.009; p = 0.004). There were no significant side effects. Conclusions:Sodium bicarbonate loading and continuous infusion was associated with a lower incidence of acute renal dysfunction in cardiac surgical patients undergoing cardiopulmonary bypass. The findings of this pilot study justify further investigation. (ClinicalTrials.gov, NCT00334191).
Courting the expert: a clash of culture?

This article reviews the utility of expert opinion in legal proceedings and the deployment of expert witnesses in adversarial litigation. The use of expert witnesses to assist courts in making just and fair conclusions may be contrasted with the partisan interests of those who call them. An adversarial system is a bad method of scientific enquiry and undermines the court's capacity to reach the ‘right’ answer. As a consequence, courts may reach the wrong conclusion based on bad science. The role of the expert as a witness places strain on an expert to provide certainty, where in fact there may be none. Recent reforms in the civil courts have changed little and the problem is even more acute in criminal trials. The expert can rely solely on the integrity of his or her own opinion, tempered with a little humility. However, when filtered through the rhetoric and advocacy of a court arena, even this may be compromised.
Pressor responses to electrical stimulation of the carotid sinus nerve in cats

Many authors (Hering, 1927; Koch 1931; Heymans, Bouckaert & Regniers, 1933; Schweitzer, 1937) describe the response of the carotid sinus nerve receptors to change of pressure in the isolated carotid sinus, and show clearly that these nerve endings act as baroceptors so that a rise of intrasinusal pressure causes, reflexly, a fall of systemic blood pressure. Action potential studies by Bronk & Stella (1932) support this view: a rise of pressure in the sinus is attended by an increased frequency of impulses in the afferent fibres of the carotid sinus nerve. It is generally agreed that the baroceptors are stimulated only by a rise of pressure in the sinus, and evidence exists that there is a threshold pressure (20-80 mm.Hg in different species) below which activation of the baroceptors does not occur (Koch, 1931; Schweitzer, 1937). In view of the large number of observations on carotid sinus function, it is perhaps surprising that there are only few observations with reference to the effects of electrical stimulation of the nerve trunk. The development of the rectangular wave electronic stimulator permits a more detailed investigation of this problem, and the present paper gives results obtained by the use of this device and of a conventional induction coil. Some of our observations have previously been reported (Neil, Redwood & Schweitzer, 1948).
Reliability of isolated isometric function measures in rat muscles composed of different fibre types

The present study investigated the absolute reliability (RAb) of isometric measures of time‐to‐peak tension (TTP), half‐rise time (½RT), half‐fall time (½FT), twitch force (TWf) tetanic force (TETf) and the sag ratio as applied to the slow soleus (SOL) and the fast‐twitch extensor digitorum longus (EDL) and medial gastrocnemius (MG) muscles of the rat hindlimb. In addition, the relationship of each individual isometric measure was examined with regard to the pattern of myosin heavy chain (MHC) isoform expression. Measures of TTP, ½RT, ½FT and sag ratio were negatively correlated with MHCIId(x) and MHCIIb (P < 0.0001), and positively correlated with MHCI (P < 0.0001). TWf and TETf were negatively correlated with MHCI content (P < 0.0001) and positively with MHCIId(x) (P < 0.0001) and MHCIIb (P < 0.001). Comparisons of isometric measures using a paired Student's t test revealed that they were not different between the right and left legs; all measures displayed high correlations between the left and right legs (r= 0.71–0.85, P < 0.0001). In contrast to standard tests of statistical significance, these functional measures exhibited a considerable range of RAb when individual muscles were studied in only one hindlimb. When averaged across all muscles, however, the ½FT, ½RT, TWf and TTP measures possessed high overall reliability; measures of TETf and sag ratio were moderately reliable. The results of this study show that the isometric measures studied possess significant predictive value with regard to MHC isoform content; the left and right legs are interchangeable but display a considerable range of reliability when only one hindlimb is studied.
Dynamical ejecta from precessing neutron star-black hole mergers with a hot, nuclear-theory based equation of state

Neutron star-black hole binaries are among the strongest sources of gravitational waves detectable by current observatories. They can also power bright electromagnetic signals (gamma-ray bursts, kilonovae), and may be a significant source of production of r-process nuclei. A misalignment of the black hole spin with respect to the orbital angular momentum leads to precession of that spin and of the orbital plane, and has a significant effect on the properties of the post-merger remnant and of the material ejected by the merger. We present a first set of simulations of precessing neutron star-black hole mergers using a hot, composition dependent, nuclear-theory based equation of state (DD2). We show that the mass of the remnant and of the dynamical ejecta are broadly consistent with the result of simulations using simpler equations of state, while differences arise when considering the dynamics of the merger and the velocity of the ejecta. We show that the latter can easily be understood from assumptions about the composition of low-density, cold material in the different equations of state, and propose an updated estimate for the ejecta velocity which takes those effects into account. We also present an updated mesh-refinement algorithm which allows us to improve the numerical resolution used to evolve neutron star-black hole mergers.
Republished: Heart failure disease management programmes: a new paradigm for research

“ The transition from a paradigm in crisis to a new one … changes some of the field's most elementary theoretical generalizations as well as many of its paradigm methods and applications. ” Thomas S Kuhn.1 Few areas of non-pharmacological research have had as much study or success as heart failure disease management programmes (HFDMPs). The first pioneering trial published 17 years ago has been followed by over 60 randomised trials and 15 meta-analyses of home, hospital or telehealth interventions.2 Thirteen of these reviews identified 15%–20% improvements in all-cause mortality, nine identified 30%–56% improvements in HF-related hospitalisation, and 10 identified reductions in all-cause readmission of 15%–25%. 2 Accordingly, guidelines recommended HFDMPs widely and enthusiastically.3 The effectiveness of these non-pharmacological interventions appears assured. Thomas Kuhn famously argued that periods of relative stability in science, known as ‘Normal Science’, are characterised by such consistent successes.1 However, these periods of scientific successes are frequently disturbed by anomalies that cannot be explained using the very approaches that produced past successes.1 Indeed, in recent years, a series of comparatively large and high-quality trials have found no or small benefits from different kinds of HFDMPs.4 Recently, the Medicare Health Support Pilot Program trial of over 250 000 patients achieved only small improvements in a third of the outcomes measured, and identified that commercial disease management programmes for patients …
L41Q polymorphism of the G protein coupled receptor kinase 5 is associated with left ventricular apical ballooning syndrome

Altered response to acute catecholamine increase in the synaptic cleft is considered to be the mechanism underlying transient left ventricular apical ballooning syndrome (LVABS). –3 Cardiac adrenergic receptors (ARs) of the b1 and b2 subtypes activate myocytes by coupling to the Ga subunit of the heterotrimeric Gs protein, but on the other hand they also promote G protein coupled receptor kinase (GRK)-mediated phosphorylation of bAR with the intent to shut-off signalling. The impact on cardiac function of genetic variants of molecules involved in the intracellular pathways of bAR signalling has been extensively investigated. –8
Regulation of kallikrein-related peptidases in the skin – from physiology to diseases to therapeutic options

Summary Kallikrein-related peptidases (KLKs) constitute a family of 15 highly conserved serine proteases, which show a tissue-specific expression profile. This made them valuable tumour expression markers. It became evident that KLKs are involved in many physiological processes like semen liquefaction and skin desquamation. More recently, we have learnt that they are involved in many pathophysiological conditions and diseases making them promising target of therapeutic intervention. Therefore, regulation of KLKs raised the interest of numerous reports. Herein, we summarise the current knowledge on KLKs regulation with an emphasis on skin-relevant KLKs regulation processes. Regulation of KLKs takes place on the level of transcription, on protease activation and on protease inactivation. A variety of protease inhibitors has been described to interact with KLKs including the irreversible serine protease inhibitors (SERPINs) and the reversible serine protease inhibitors of Kazal-type (SPINKs). In an attempt to integrate current knowledge, we propose that KLK regulation has credentials as targets for therapeutic intervention.
Performance of the Vertical Position in Synchronized Swimming as a Function of Skill, Proprioceptive and Visual Feedback

This experiment assessed the efficacy of proprioceptive and visual information for the performance of “vertical position” by synchronized swimmers. Three skill groups of 5 senior, 5 intermediate, and 5 novice synchronized swimmers performed 40 vertical positions under four conditions. The conditions were: self-initiated with and without vision, and following experimenter perturbation, with and without vision. The dependent measure was degrees of error from true vertical. Analysis indicated that either proprioception or proprioception and vision may be used in performing vertical positions. A significant main effect was found among skill groups.
Correlative Microscopy Using FluoroNanogold on Ultrathin Cryosections: Proof of Principle

We demonstrate a fluorescent ultrasmall immunogold probe, FluoroNanogold (FNG), to be a versatile reporter system for immunocytochemical labeling of ultrathin cryosections. FNG-labeled molecules in the same ultrathin cryosections can be resolved by two imaging techniques (i.e., fluorescence and electron microscopy). Lactoferrin, a marker protein for the specific granules in human neutrophils, was employed as the target for FNG immunolabeling. The spatial resolution of the fluorescence signal from FNG-labeled specific granules was compatible with that of silver-enhanced gold signal from the same granules in electron microscopy. Our results confirm that FNG can be used as a probe for highresolution correlation between immunofluorescence and electron microscopy.
Effects of Cover Object Spacing on the Socioecology of the Red-Backed Salamander, Plethodon cinereus

Abstract Territoriality has been well-documented in terrestrial plethodontid salamanders. However, most studies of territoriality have focused either on defense of single cover objects or on defense of areas of forest floor. In nature, cover objects tend to occur in groups, and little is known about how cover-object distributions affect territory defense and salamander spatial associations. We manipulated cover-object spacing within a home range and used mark–recapture data to examine the effects of these manipulations on intra- and intersexual spatial associations in the red-backed salamander, Plethodon cinereus. Similar total numbers of salamanders were found in the different treatments, and salamanders moved between cover objects with similar frequency regardless of cover-object spacing. However, male spatial associations were affected by cover-object spacing, with males never found simultaneously under adjacent cover objects. Furthermore, the spatial associations of males and females differed among the cover-object spacing treatments. Males and females shared the same cover object 76% of the time when cover objects were adjacent, but only 37% of the time when cover objects were separated by 1 m. Our results suggest that P. cinereus often use multiple cover objects within a home range, and that males may defend these while they are using them. Additionally, males and females appear to adjust their use of cover objects with respect to the home ranges of opposite sex salamanders.
Effect of Thiopental Induction on Sympathetic Activity

Several recent studies with different anesthetic agents have reported increases in plasma norepinephrine concentration during induction. To determine if induction with intravenous injection of thiopental also is associated with initial sympathetic activation, 24 ASA class I patients were assigned randomly to receive one of the following anesthetics: Group I, thiopental 3 rag/kg, iv, followed by inhalation of 100% oxygen and a continuous intravenous infusion of thiopental 0.2–0.3 mg · kg-1 · min-1; Group II, thiopental 3 mg/kg followed by inhalation of halothane (1.5% end-tidal concentration) in oxygen; and Group III, thiopental 3 mg/kg followed by inhalation of 70% nitrous oxide in oxygen. After thiopental injection, ventilation was controlled to maintain Pco2 near control levels. In Group I, plasma norepinephrine concentration decreased with continued administration of thiopental. This decrease became statistically significant (P < 0.05) 10 min after injection. Plasma epinephrine concentration did not change. For Groups II and III, both plasma norepinephrine and epinephrine concentration did not change. For Groups II and III, the stability of the catecholamine concentrations during induction may have been caused by the circumvention of the second stage of anesthesia, equal depression of both inhibitory and excitatory synapses, or the combined effects of the agents. Regardless of the cause, the use of a modest induction dose of thiopental appears to allow the induction of anesthesia without sympathetic activation. When it is important to prevent sympathetic activation, administering a modest dose of thiopental before the inhalation of halothane or nitrous oxide may be preferable to inducing anesthesia with inhalation agents or narcotics alone.
Lexical Quality and Eye Movements: Individual Differences in the Perceptual Span of Skilled Adult Readers

Two experiments used the gaze-contingent moving-window paradigm to investigate whether reading comprehension and spelling ability modulate the perceptual span of skilled adult readers during sentence reading. Highly proficient reading and spelling were both associated with increased use information to the right of fixation, but did not systematically modulate the extraction of information to the left of fixation. Individuals who were high in both reading and spelling ability showed the greatest benefit from window sizes larger than 11 characters, primarily because of increases in forward saccade length. They were also significantly more disrupted by being denied close parafoveal information than those poor in reading and/or spelling. These results suggest that, in addition to supporting rapid lexical retrieval of fixated words, the high quality lexical representations indexed by the combination of high reading and spelling ability support efficient processing of parafoveal information and effective saccadic targeting.