Miracle-dz/UniFAR-FTUs huggingface dataset:
Large-scale SOD1 mutation screening provides evidence for genetic heterogeneity in amyotrophic lateral sclerosis

Objective To estimate the frequency of SOD1 mutations in a large referral cohort of familial amyotrophic lateral sclerosis (FALS) and sporadic amyotrophic lateral sclerosis (SALS) patients from The Netherlands and to compare this frequency with that of other developed countries. Methods A total of 451 sporadic and 55 FALS patients were screened for SOD1 mutations. The authors performed PCR amplification of all five coding exons of SOD1 followed by direct DNA sequencing using forward and reverse primers. Results One novel mutation (p.I99V) and a homozygous p.D90A mutation were identified in SALS patients. In a pedigree with Mendelian dominant FALS, one patient was found to be heterozygous for the p.D90A mutation. SOD1 mutation frequency was found to be significantly lower in The Netherlands compared with other countries with p=0.0004 for FALS (21.9% vs 2.5%) and p=0.005 for SALS (2.5% vs 0.44%). Conclusions The authors demonstrate that SOD1 mutations are rare in The Netherlands in familial and SALS. This observation suggests that the genetic background of amyotrophic lateral sclerosis differs between different populations, countries and regions. This may have consequences for the interpretation of association studies and explain why replication of association studies has proven difficult in amyotrophic lateral sclerosis.
[Clinical characteristics of juvenile dermatomyositis].

INTRODUCTION Dermatomyositis, belonging to the group of the idiopathic inflammatory myopathies, is characterized by bimodal pattern of age-specific incidence of rates, with peaks in age group from 5 to 14 years (juvenile dermatomyositis) and in age group from 45 to 64 years (adult dermatomyositis). THE AIM OF THIS STUDY Is to evaluate the clinical characteristics of 12 patients with juvenile dermatomyositis followed by the 3rd Department of Internal Medicine, University of Debrecen and the 2nd Department of Pediatrics, Semmelweis University, Budapest. METHODS The authors analyzed the medical records of the patients with juvenile and adult form of dermatomyositis retrospectively. RESULTS All of the children had symmetrical weakness of the proximal muscles. The most frequent cutaneous features were facial erythema and Gottron papules (11/12). The extramuscular manifestations were also assessed. 7 children had arthralgia. There were observed pulmonary fibrosis, Raynaud-syndrome, dysphagia and sicca-syndrome in the same patient, whose disease is overlapped with progressive systemic sclerosis. In view of the clinical course, the authors found that prevalence of polycyclic (relapsing-remitting) and monophasic subtypes of the disease were similar (6/12 and 5/12). Finally, all of the patients achieved remission, however, 2 patients have to take low-dose corticosteroid therapy permanently to maintain remission. One patient's cutaneous symptoms proved to be persistent and in further 2 cases, regression of the calcinosis is slow, but continuous. DISCUSSION The authors compare their data of juvenile patients with the data of the relevant literature and to their experience with the management of adult DM patients. It seems to be reasonable to treat the patients in centres.
The afferent glomerular arteriole: immunocytochemical and electrophysiological investigations.

Immunocytochemical techniques were used for the localization of the different components of the renin-angiotensin system (RAS) within the kidneys of various species. Special attention was paid to the renin-secreting granulated cells located mainly in the media of the afferent glomerular arteriole. It was demonstrated that variations of kidney renin caused by stimulation or inhibition of the RAS are reflected in changes of the length of the renin-positive part of the afferent arteriole upstream from its entry into the glomerulus. During stimulation, plain smooth-muscle cells are transformed into renin-generating granulated cells. Likewise, the marked species differences in kidney renin are paralleled by corresponding differences in the renin-positive part of the afferent vessel. In this context, the site of action and the relative importance of the stimuli inducing renin secretion, i.e., the beta 1-adrenoreceptor, the mechanoreceptor, and the so-called macula densa mechanism are discussed. Whereas the microtopography of the RAS in the kidney has been at least partly understood, little is known about the stimulus-secretion coupling at the level of the individual granulated cell. Thus, adequate electrophysiological data about granulated cells might help to understand some still obscure phenomena, e.g., the inhibitory effect of Ca2+ on renin secretion. Our investigations in the hydronephrotic kidney preparation of the mouse show that granulated cells do not differ significantly from "plain" smooth-muscle cells in their electrical characteristics. They have a membrane potential of -55 mV and are spontaneously active. Both cell types are depolarized by noradrenaline and angiotensin II (AII), although they remain unaffected by isoproterenol. Since isoproterenol is known to stimulate renin secretion, our results indicate that stimulus-secretion coupling via the beta 1-adrenoreceptor is likely to proceed without changes of membrane potential in granulated cells.
Simmelian Ties and Structural Holes: Exploring Their Topological Roles in Forming Trust for Securing Wireless Sensor Networks

Due to the nature of wireless sensor networks (WSNs) in open-access and error-prone wireless environments, the security issues are always crucial. The traditional security mechanisms such as Public Key Infrastructure (PKI) is no longer as feasible in protecting WSN as in wired networks. The new concept of trust has emerged in recent studies as an alternative mechanism to address the security concerns in WSNs. Most recent studies on trust are mainly focused on how to model and evaluate trust so as to effectively detect, isolate, and avoid any malicious activity in the network. In this paper, we have introduced the new angle of adaptive network approach to study 'dynamics on networks' i.e., trust state transition on a network with a fixed topology or 'dynamics of networks' i.e., topological transformation of a network with no dynamic trust state changes separately so as to discover the interplay between network overlay entities' trust evaluation and its underlie topological connectivity. Inspired from the trust studies in sociology, we propose that the Simmelian tie structured networks enable more positive impact on fostering trustworthiness among sensor nodes, while structural hole characterized networks provide more opportunity for misbehaviors and have negative impact to secure WSNs. These hypothesis have been confirmed by the extensive simulation studies.
Effect of montelukast on exhaled NO in asthmatic children exposed to relevant allergens

The level of exhaled nitric oxide (FENO) is increased in house dust mite (HDM)‐sensitized asthmatic children after exposure to HDM antigen, and inhaled steroids can prevent this increase. The aim of this study was to evaluate whether montelukast could prevent an increase in FENO levels in allergic asthmatic children after a brief period of exposure to relevant allergens. Sixteen children were evaluated at the residential house ‘Istituto Pio XII’ (Misurina, Bellunio, Italy) in the Italian Alps, a dust mite‐free environment. FENO levels were evaluated before (t0) and immediately after (t1) the children were exposed to HDM allergens for 2 weeks in their homes at sea level. No significant difference in FENO was observed in the fluticasone‐treated group of children after 2 weeks at sea level. In the group treated with montelukast, an increase in FENO was observed between t0 and t1, which failed to reach statistical significance. These preliminary data suggest that oral montelukast could be effective in preventing the relapse in airway inflammation in allergic asthmatic children who are occasionally exposed to relevant allergens for a short period of time.
The impact of 24 h consultant shop floor presence on emergency department performance: a natural experiment

Objectives As a result of gaps in middle-grade cover in the emergency department it became necessary for consultants to work some night shifts. This study aimed to examine the effect of this change in practice on performance. Methods A prospective observational study was conducted. Staffing and workload variables were collected over a period of 6 months in a single district general emergency department. The outcomes assessed were process times, the proportion of patients admitted and the proportion of patients returning within 7 days. Results Consultants worked 26 of 182 night shifts during the period studied. There were no differences in the number of patients present in the department at the start of the middle-grade or consultant night shifts. Fewer patients presented per hour during middle-grade night shifts: 3.8 patients per hour versus 4.4 patients per hour during consultant nights. Compared with middle-grade night shifts, the median waiting time was on average 19.6 min less and the median emergency department length of stay was 20.5 min less during consultant night shifts. The proportion of patients admitted from the emergency department was on average 3.9% less than during middle-grade night shifts but there was no difference in the proportion returning within 7 days. Conclusion In this small single-site study, a consultant working nights has been shown to reduce process times and the rate of admission. It remains unclear whether such improvements would be sustained in the longer term.
Preventing recurrent homelessness among mentally ill men: a "critical time" intervention after discharge from a shelter.

OBJECTIVES This study examined a strategy to prevent homelessness among individuals with severe mental illness by providing a bridge between institutional and community care. METHODS Ninety-six men with severe mental illness who were entering community housing from a shelter institution were randomized to receive 9 months of a "critical time" intervention plus usual services or usual services only. The primary analysis compared the mean number of homeless nights for the two groups during the 18-month follow-up period. To elucidate time trends, survival curves were used. RESULTS Over the 18-month follow-up period, the average number of homeless nights was 30 for the critical time intervention group and 91 for the usual services group. Survival curves showed that after the 9-month period of active intervention, the difference between the two groups did not diminish. CONCLUSIONS Strategies that focus on a critical time of transition may contribute to the prevention of recurrent homelessness among individuals with mental illness, even after the period of active intervention.
The Stable, Functional Core of DdrA from Deinococcus radiodurans R1 Does Not Restore Radioresistance In Vivo

ABSTRACT DdrA protein binds to and protects 3′ DNA ends and is essential for preserving the genome integrity of Deinococcus radiodurans following treatment by gamma radiation in an environment lacking nutrients. Limited proteolysis was used to identify a stable and functional protein core, designated DdrA157, consisting of the first 157 residues of the protein. In vitro, the biochemical differences between wild-type and mutant proteins were modest. DdrA exhibits a strong bias in binding DNA with 3′ extensions but not with 5′ extensions. The mutant DdrA157 exhibited a greater affinity for 5′ DNA ends but still bound to 3′ ends more readily. However, when we replaced the wild-type ddrA gene with the mutant gene for ddrA157, the resulting D. radiodurans strain became almost as sensitive to gamma radiation as the ddrA knockout strain. These results suggest that while the stable protein core DdrA157 is functional for DNA binding and protection assays in vitro, the carboxyl terminus is required for important functions in vivo. The C terminus may therefore be required for protein or DNA interactions or possibly as a regulatory region for DNA binding or activities not yet identified.
First-Ever Stroke and Outcome in Patients Admitted to Perugia Stroke Unit: Predictors for Death, Dependency, and Recurrence of Stroke within the First Three Months

Predictors of poor outcome after first-ever stroke within 3 months in consecutive patients admitted to our Stroke Unit were defined. Factors included age, sex, risk factors, occurrence of transient ischemic attacks, extension of cerebral infarction, presumed cause of stroke, clinical findings, and demographic characteristics. Multiple regression models were used to analyze predictors of mortality, dependency and stroke recurrence. A total of 435 patients with first-ever stroke were included. Of these, 358 patients had ischemic stroke and 77 hemorrhagic stroke. Three-month mortality rate was 20.5%. After the same period, 24.6% of survivors were dependent (mRS ≥3) and 5.0% of patients had recurrent stroke. Age, the presence of atrial fibrillation, impaired consciousness on admission, and stroke severity were related to mortality. The presence of stroke due to an undetermined cause or small vessel disease was associated with lower mortality. Partial anterior circulation syndrome or lacunar syndrome were both related to better outcome. The best predictors for dependency after 3 months were age and stroke severity. The only variable identified as the best predictor for recurrence was the presence of diabetes mellitus.
Ringers lactate vs Normal saline for children with acute diarrhea and severe dehydration- a double blind randomized controlled trial.

OBJECTIVE WHO recommends Ringers lactate (RL) and Normal Saline (NS) for rapid intravenous rehydration in childhood diarrhea and severe dehydration. We compared these two fluids for improvement in pH over baseline during rapid intravenous rehydration in children with acute diarrhea. DESIGN Double-blind randomized controlled trial SETTING Pediatric emergency facilities at a tertiary-care referral hospital. INTERVENTION Children with acute diarrhea and severe dehydration received either RL (RL-group) or NS (NS-group), 100 mL/kg over three or six hours. Children were reassessed after three or six hours. Rapid rehydration was repeated if severe dehydration persisted. Blood gas was done at baseline and repeated after signs of severe dehydration disappeared. OUTCOME MEASURES Primary outcome was change in pH from baseline. Secondary outcomes included changes in serum electrolytes, bicarbonate levels, and base-deficit from baseline; mortality, duration of hospital stay, and fluids requirement. RESULTS Twenty two children, 11 each were randomized to the two study groups. At primary end point (disappearance of signs of severe dehydration), the improvement in pH from baseline was not significant in RL-group [from 7.17 (0.11) to 7.28 (0.09)] as compared to NS-group [7.09 (0.11) to 7.21 (0.09)], P=0.17 (after adjusting for baseline serum Na/ Cl). Among this limited sample size, children in RL group required less fluids [median 310 vs 530 mL/kg, P=0.01] and had shorter median hospital stay [38 vs 51 hours, P=0.03]. CONCLUSIONS There was no difference in improvement in pH over baseline between RL and NS among children with acute diarrhea and severe dehydration.
Axonal projections from the lateral and medial superior olive to the inferior colliculus of the cat: A study using electron microscopic autoradiography

The superior olivary complex is the first site in the central auditory system where binaural interactions occur. The output of these nuclei is direct to the central nucleus of the inferior colliculus, where binaural inputs synapse with monaural afferents such as those from the cochlear nuclei. Despite the importance of the olivary pathways for binaural information processing, little is known about their synaptic organization ir the colliculus. The present study investigates the structure of the projections from the lateral and medial superior olivary nuclei to the inferior colliculus at the electron microscopic level. Stereotaxic placement and electrophysi ological responses to binaural sounds were used to locate the superior olive. Anterograde axonal transport of 3H‐leucine was combined with light and electron microscopic autoradiography to reveal the location and morphology of the olivary axonal endings.
Globus Pallidus Neurons Dynamically Regulate the Activity Pattern of Subthalamic Nucleus Neurons through the Frequency-Dependent Activation of Postsynaptic GABAA and GABAB Receptors

Reciprocally connected GABAergic neurons of the globus pallidus (GP) and glutamatergic neurons of the subthalamic nucleus (STN) are a putative generator of pathological rhythmic burst firing in Parkinson's disease (PD). Burst firing of STN neurons may be driven by rebound depolarization after barrages of GABAA receptor (GABAAR)-mediated IPSPs arising from pallidal fibers. To determine the conditions under which pallidosubthalamic transmission activates these and other postsynaptic GABARs, a parasagittal mouse brain slice preparation was developed in which pallidosubthalamic connections were preserved. Intact connectivity was first confirmed through the injection of a neuronal tracer into the GP. Voltage-clamp and gramicidin-based perforated-patch current-clamp recordings were then used to study the relative influences of GABAAR- and GABABR-mediated pallidosubthalamic transmission on STN neurons. Spontaneous phasic, but not tonic, activation of postsynaptic GABAARs reduced the frequency and disrupted the rhythmicity of autonomous firing in STN neurons. However, postsynaptic GABABRs were only sufficiently activated to impact STN firing when pallidosubthalamic transmission was elevated or pallidal fibers were synchronously activated by electrical stimulation. In a subset of neurons, rebound burst depolarizations followed high-frequency, synchronous stimulation of pallidosubthalamic fibers. Although GABABR-mediated hyperpolarization was itself sufficient to generate rebound bursts, coincident activation of postsynaptic GABAARs produced longer and more intense burst firing. These findings elucidate a novel route through which burst activity can be generated in the STN, and suggest that GABARs on STN neurons could act in a synergistic manner to generate abnormal burst activity in PD.
Unilateral ECT: Advantages and Efficacy in the Treatment of Depression

Electroconvulsive therapy is an efficacious treatment for some acute or drug resistant psychiatric disorders. However, there is some concern with memory impairment and brain damage and in order to decrease these complications, some changes to the technical aspect of electroconvulsive therapy were implemented during the last few decades. One of the major changes is the use of unilateral electrical stimulation on the non-dominant hemisphere which leads to less memory impairment and faster recovery time of cognitive functions. However, for optimal efficacy several variables have to be understood and integrated: electrodes placement, interelectrodes distance, waveform stimuli.
Real Interest Rates, Imbalances and the Curse of Regional Safe Asset Providers at the Zero Lower Bound

The current environment is characterized by low real rates and by policy rates close to or at their lower bound in all major financial areas. We analyze these unusual economic conditions from a historical perspective and draw some implications for external imbalances, safe asset demand and the process of external adjustment. First, we decompose the fluctuations in the world consumption wealth ratio over long period of times and show that they anticipate movements of the real rate of interest. Second, our estimates suggest that the world real rate of interest is likely to remain low or negative for an extended period of time. In this context, we argue that there is a renewed Triffin dilemma where safe asset providers face a trade-off in terms of external exposure and real appreciation of their currency. This trade-off is particularly acute for smaller economies. This is the `curse of the regional safe asset provider. ' We discuss how this `curse' is playing out for two prominent regional safe asset providers: core EMU and Switzerland.
Is Eucalyptus Cryptically Self-incompatible?

BACKGROUND AND AIMS The probability that seeds will be fertilized from self- versus cross-pollen depends strongly on whether plants have self-incompatibility systems, and how these systems influence the fate of pollen tubes. METHODS In this study of breeding systems in Eucalyptus urophylla and Eucalyptus grandis, epifluorescence microscopy was used to study pollen tube growth in styles following self- and cross-pollinations. KEY RESULTS Pollen tubes from self-pollen took significantly longer than those from cross-pollen to grow to the base of the style in both E. urophylla (120 h vs. 96 h) and E. grandis (96 h vs. 72 h). In addition, both species exhibited reduced seed yields following self-pollination compared with cross-pollination. CONCLUSIONS The present observations suggest that, in addition to a late-acting self-incompatibility barrier, cryptic self-incompatibility could be a mechanism responsible for the preferential out-crossing system in these two eucalypt species.
A Comparison between Novices and Experts of the Velocity-Accuracy Trade-Off in Overarm Throwing

Expert team-handball players do not show the typical trade-off between speed and accuracy in overarm throwing. Van den Tillaar and Ettema (2003a) attributed this result to the uniqueness of the training experience of this group. The purpose of this study was to test their hypothesis by comparing experts with novices on overarm throwing by manipulating the goal of the task using different instructions. No trade-off between speed and accuracy was found for novices (n = 13; M age = 22.7 yr., SD = 2.2) or experts (n = 9; M age = 24 yr., SD = 2.2): accuracy did not change by instruction. Furthermore, the linear velocities of the ball and endpoints of body segments and their timing were affected by instruction in a similar fashion in both groups. This finding indicates that training experience is not related to speed-accuracy tradeoff in overarm throwing.
Assessing new developments in the pre-market regulatory process of medical devices in the People’s Republic of China

The objective of this paper is to provide a systematic overview of the Chinese medical device registration processes, identify challenges and suggest how these can be addressed. In addition, the paper will outline the impact of new policies and regulations since the restructuring of the China FDA. A systematic review was performed for journal articles between the year of 2009 and 2013 in the following databases: PubMed, ScienceDirect and Zhongguozhiwang. The review has identified 184 papers which were potentially relevant. Seventeen articles were included in the review, which highlights the challenges and opportunities related to the medical device registration process. In order to understand the actual impact of the regulation environment and its policies including the lack of regulatory guidance regular assessment updates are crucial. The results of this paper are aimed at informing regulatory bodies, health policy decision makers, national and international Health Technology Assessment networks as well as medical devices manufacturers.
Does Private Schooling Increase Adult Earnings? Cohort-Level Evidence for U.S. States

Public schooling in the U.S. has numerous critics, many of whom suggest that alternatives such as providing vouchers for private schools may be more effective. This paper combines decennial census and American Community Survey data for various years to examine the relationship between cohort-level private schooling rates and later earnings during adulthood. We also explore differences by sex and examine the role played by the quantity of education completed and occupational attainment. We find a significant positive relationship between private schooling rates and adult earnings for women but a small relationship for men.