bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prolonged-Release Fampridine as Adjunct Therapy to Active Motor Training in MS Patients: A Pilot, Double-Blind, Randomized, Placebo-Controlled Study
Authors: Jacques François , Schembri Adrian , Nativ Avi , Paquette Chantal , Kalinowski Pawel 
Published: March 2018

Background Both prolonged-release fampridine (PRF) and enabling active motor training (EAMT) are beneficial in multiple sclerosis (MS) patients. Their combined effect is, however, understudied. Objective The objective of this paper is to determine if PRF augments the beneficial effect of EAMT in MS patients as opposed to placebo. Method This is a pilot, randomized, placebo-controlled, double-blind 14-week study. Participants were randomly assigned to receive PRF 10 mg BID ( n = 21) or placebo ( n = 20). All patients underwent EAMT during the first six weeks. Patients were assessed at –4, 0, 6 and 14 weeks. Results Both groups remained stable between –4 to 0 weeks and showed statistically significant improvements for the six-minute walk and the five-times-sit-to-stand test at weeks 6 and 14. The PRF-treated group achieved a greater mean percentage improvement and a higher incidence of responders in all three tasks at both time points. The study was, however, underpowered to reach statistical significance. Conclusion Our results confirm previous studies demonstrating that MS patients, despite significant disability, do benefit from a rehabilitation program. Our study is the first to show a trend suggesting that PRF in MS patients appears to enhance the benefit of EAMT. Further studies are required to confirm this. Clinical trial registration number with Clinicaltrial.gov: NCT02146534
Unmet Needs for Care and Medications, Cost as a Reason for Unmet Needs, and Unmet Needs as a Big Problem, due to Health-Care Provider (Dis)Continuity
Authors: Stransky Michelle L 
Published: March 2018

Objective: Provider discontinuity is associated with poorer health-care outcomes compared to continuity in studies using retrospective reports of provider (dis)continuity. This study examined unmet needs for care and assessed cost as the reason for and the level of the problem resulting from unmet needs by provider (dis)continuity using longitudinal data. Methods: Pooled data on 10 714 working-age adults (aged 18-64) from the Medical Expenditure Panel Survey (panels 16 [2011-2012] and 17 [2012-2013]) were analyzed. Provider (dis)continuity was defined by 2 reports of having a health-care provider during the period. Results: Persons who lost providers were more likely to forego medical care and prescription medications, forego care due to cost, and report that delaying care was a big problem than their peers who experienced continuity. Persons who gained providers were more likely to delay dental care than those who always had, lost, or never had providers. Conclusions: Persons who experience discontinuity have poorer access to care than their peers who experience continuity. Public health initiatives should promote longitudinal relationships between persons and health-care providers.
Cancer and platelet crosstalk: opportunities and challenges for aspirin and other antiplatelet agents
Authors: Xu Xiaohong Ruby , Yousef George M. , Ni Heyu 
Published: March 2018

Abstract
Platelets have long been recognized as key players in hemostasis and thrombosis; however, growing evidence suggests that they are also significantly involved in cancer, the second leading cause of mortality worldwide. Preclinical and clinical studies showed that tumorigenesis and metastasis can be promoted by platelets through a wide variety of crosstalk between platelets and cancer cells. For example, cancer changes platelet behavior by directly inducing tumor-platelet aggregates, triggering platelet granule and extracellular vesicle release, altering platelet phenotype and platelet RNA profiles, and enhancing thrombopoiesis. Reciprocally, platelets reinforce tumor growth with proliferation signals, antiapoptotic effect, and angiogenic factors. Platelets also activate tumor invasion and sustain metastasis via inducing an invasive epithelial-mesenchymal transition phenotype of tumor cells, promoting tumor survival in circulation, tumor arrest at the endothelium, and extravasation. Furthermore, platelets assist tumors in evading immune destruction. Hence, cancer cells and platelets maintain a complex, bidirectional communication. Recently, aspirin (acetylsalicylic acid) has been recognized as a promising cancer-preventive agent. It is recommended at daily low dose by the US Preventive Services Task Force for primary prevention of colorectal cancer. The exact mechanisms of action of aspirin in chemoprevention are not very clear, but evidence has emerged that suggests a platelet-mediated effect. In this article, we will introduce how cancer changes platelets to be more cancer-friendly and highlight advances in the modes of action for aspirin in cancer prevention. We also discuss the opportunities, challenges, and opposing viewpoints on applying aspirin and other antiplatelet agents for cancer prevention and treatment.
Markers of neutrophil extracellular traps predict adverse outcome in community-acquired pneumonia: secondary analysis of a randomised controlled trial
Authors: Ebrahimi Fahim , Giaglis Stavros , Hahn Sinuhe , Blum Claudine A. , Baumgartner Christine , Kutz Alexander , van Breda Shane Vontelin , Mueller Beat , Schuetz Philipp , Christ-Crain Mirjam , Hasler Paul 
Published: March 2018

Neutrophil extracellular traps (NETs) are a hallmark of the immune response in inflammatory diseases. However, the role of NETs in community-acquired pneumonia (CAP) is unknown. This study aims to characterise the impact of NETs on clinical outcomes in pneumonia.This is a secondary analysis of a randomised controlled, multicentre trial. Patients with CAP were randomly assigned to either 50 mg prednisone or placebo for 7 days. The primary end-point was time to clinical stability; main secondary end-points were length of hospital stay and mortality.In total, 310 patients were included in the analysis. Levels of cell-free nucleosomes as surrogate markers of NETosis were significantly increased at admission and declined over 7 days. NETs were significantly associated with reduced hazards of clinical stability and hospital discharge in multivariate adjusted analyses. Moreover, NETs were associated with a 3.8-fold increased adjusted odds ratio of 30-day mortality. Prednisone treatment modified circulatory NET levels and was associated with beneficial outcome.CAP is accompanied by pronounced NET formation. Patients with elevated serum NET markers were at higher risk for clinical instability, prolonged length of hospital stay and 30-day all-cause mortality. NETs represent a novel marker for outcome and a possible target for adjunct treatments of pneumonia.
Rates of change in FEV1andDLCOas potential indicators for mTOR inhibitor therapy in premenopausal lymphangioleiomyomatosis patients
Authors: Taveira-DaSilva Angelo M. , Julien-Williams Patricia , Jones Amanda M. , Stylianou Mario , Moss Joel 
Published: March 2018

The value of rates of change in forced expiratory volume in 1 s (FEV1) and diffusing capacity of the lung for carbon monoxide (DLCO) to predict disease progression, and initiation of mTOR (mechanistic target of rapamycin) inhibitor therapy has not been evaluated.In 84 premenopausal lymphangioleiomyomatosis patients, individual rates of change in FEV1andDLCOand their 95% confidence intervals were used to derive subsequent lowest values of FEV1andDLCOthat would prompt initiation of sirolimus therapy. These treatment criteria were compared with a criterion based on FEV1orDLCO≤70% predicted. In 12 patients undergoing sirolimus therapy both methods for determining the optimal point for initiation of therapy were evaluated.27 and 35 patients who experienced greater than expected rates of change in FEV1andDLCO, respectively, would have been excluded from therapy based on an FEV1orDLCO>70% pred. 25 of the 84 patients were eventually treated, but only when FEV1orDLCOwere ≤70% pred. Applying such treatment criteria to 12 patients undergoing sirolimus therapy would have delayed treatment for many years.Premenopausal females in whom FEV1orDLCOare declining at rates above the expected based on their individual rates of decline, should be considered for sirolimus therapy before the FEV1orDLCOfalls to ≤70% pred.
Impact of sleep alterations on weaning duration in mechanically ventilated patients: a prospective study
Authors: Thille Arnaud W. , Reynaud Faustine , Marie Damien , Barrau Stéphanie , Rousseau Ludivine , Rault Christophe , Diaz Véronique , Meurice Jean-Claude , Coudroy Rémi , Frat Jean-Pierre , Robert René , Drouot Xavier 
Published: March 2018

Sleep is markedly altered in intensive care unit (ICU) patients and may alter respiratory performance. Our objective was to assess the impact of sleep alterations on weaning duration.We conducted a prospective physiological study at a French teaching hospital. ICU patients intubated for at least 24 h and difficult to wean were included. Complete polysomnography (PSG) was performed after the first spontaneous breathing trial failure. Presence of atypical sleep, duration of sleep stages, particularly rapid eye movement (REM) sleep, and electroencephalogram (EEG) reactivity at eyes opening were assessed by a neurologist.20 out of 45 patients studied (44%) had atypical sleep that could not be classified according to the standard criteria. Duration of weaning between PSG and extubation was significantly longer in patients with atypical sleep (median (interquartile range) 5 (2–8)versus2 (1–2) days; p=0.001) and in those with no REM sleep compared with the others. Using multivariate logistic regression analysis, atypical sleep remained independently associated with prolonged weaning (>48 h after PSG). Altered EEG reactivity at eyes opening was a good predictor of atypical sleep.Our results suggest for the first time that brain dysfunction may have an influence on the ability to breathe spontaneously.
FGF signaling controls Shh-dependent oligodendroglial fate specification in the ventral spinal cord
Authors: Farreny Marie-Amélie , Agius Eric , Bel-Vialar Sophie , Escalas Nathalie , Khouri-Farah Nagham , Soukkarieh Chadi , Danesin Cathy , Pituello Fabienne , Cochard Philippe , Soula Cathy 
Published: March 2018

Abstract

Background
Most oligodendrocytes of the spinal cord originate from ventral progenitor cells of the pMN domain, characterized by expression of the transcription factor Olig2. A minority of oligodendrocytes is also recognized to emerge from dorsal progenitors during fetal development. The prevailing view is that generation of ventral oligodendrocytes depends on Sonic hedgehog (Shh) while dorsal oligodendrocytes develop under the influence of Fibroblast Growth Factors (FGFs).

Results
Using the well-established model of the chicken embryo, we show that ventral spinal progenitor cells activate FGF signaling at the onset of oligodendrocyte precursor cell (OPC) generation. Inhibition of FGF receptors at that time appears sufficient to prevent generation of ventral OPCs, highlighting that, in addition to Shh, FGF signaling is required also for generation of ventral OPCs. We further reveal an unsuspected interplay between Shh and FGF signaling by showing that FGFs serve dual essential functions in ventral OPC specification. FGFs are responsible for timely induction of a secondary Shh signaling center, the lateral floor plate, a crucial step to create the burst of Shh required for OPC specification. At the same time, FGFs prevent down-regulation of Olig2 in pMN progenitor cells as these cells receive higher threshold of the Shh signal. Finally, we bring arguments favoring a key role of newly differentiated neurons acting as providers of the FGF signal required to trigger OPC generation in the ventral spinal cord.

Conclusion
Altogether our data reveal that the FGF signaling pathway is activated and required for OPC commitment in the ventral spinal cord. More generally, our data may prove important in defining strategies to produce large populations of determined oligodendrocyte precursor cells from undetermined neural progenitors, including stem cells. In the long run, these new data could be useful in attempts to stimulate the oligodendrocyte fate in residing neural stem cells.
Function and evolution of specialized endogenous lipids in toothed whales
Authors: Koopman Heather N. 
Published: March 2018

ABSTRACTThe Odontocetes (toothed whales) possess two types of specialized fat and, therefore, represent an interesting group when considering the evolution and function of adipose tissue. All whales have a layer of superficial blubber, which insulates and streamlines, provides buoyancy and acts as an energy reserve. Some toothed whales deposit large amounts of wax esters, rather than triacylglycerols, in blubber, which is unusual. Waxes have very different physical and physiological properties, which may impact blubber function. The cranial acoustic fat depots serve to focus sound during echolocation and hearing. The acoustic fats have unique morphologies; however, they are even more specialized biochemically because they are composed of a mix of endogenous waxes and triacylglycerols with unusual branched elements (derived from amino acids) that are not present in other mammals. Both waxes and branched elements alter how sound travels through a fat body; they are arranged in a 3D topographical pattern to focus sound. Furthermore, the specific branched-chain acid/alcohol synthesis mechanisms and products vary phylogenetically (e.g. dolphins synthesize lipids from leucine whereas beaked whales use valine). I propose that these specialized lipids evolved first in the head: wax synthesis first emerged to serve an acoustic function in toothed whales, with branched-chain synthesis adding additional acoustic focusing power, and some species secondarily retained wax synthesis pathways for blubber. Further research is necessary to elucidate specific molecular mechanisms controlling the synthesis and deposition of wax esters and branched-chain fatty acids, as well as their spatial deposition within tissues and within adipocytes.
Adiposity and fat metabolism during combined fasting and lactation in elephant seals
Authors: Fowler Melinda , Champagne Cory , Crocker Daniel 
Published: March 2018

ABSTRACT
Animals that fast depend on mobilizing lipid stores to power metabolism. Northern elephant seals (Mirounga angustirostris) incorporate extended fasting into several life-history stages: development, molting, breeding and lactation. The physiological processes enabling fasting and lactation are important in the context of the ecology and life history of elephant seals. The rare combination of fasting and lactation depends on the efficient mobilization of lipid from adipose stores and its direction into milk production. The mother elephant seal must ration her finite body stores to power maintenance metabolism, as well as to produce large quantities of lipid and protein-rich milk. Lipid from body stores must first be mobilized; the action of lipolytic enzymes and hormones stimulate the release of fatty acids into the bloodstream. Biochemical processes affect the release of specific fatty acids in a predictable manner, and the pattern of release from lipid stores is closely reflected in the fatty acid content of the milk lipid. The content of the milk may have substantial developmental, thermoregulatory and metabolic consequences for the pup. The lactation and developmental patterns found in elephant seals are similar in some respects to those of other mammals; however, even within the limited number of mammals that simultaneously fast and lactate, there are important differences in the mechanisms that regulate lipid mobilization and milk lipid content. Although ungulates and humans do not fast during lactation, there are interesting comparisons to these groups regarding lipid mobilization and milk lipid content patterns.
Fructose-containing caloric sweeteners as a cause of obesity and metabolic disorders
Authors: Tappy Luc 
Published: March 2018

ABSTRACTCompared with other carbohydrates, fructose-containing caloric sweeteners (sucrose, high-fructose corn syrup, pure fructose and fructose-glucose mixtures) are characterized by: a sweet taste generally associated with a positive hedonic tone; specific intestinal fructose transporters, i.e. GLUT5; a two-step fructose metabolism, consisting of the conversion of fructose carbones into ubiquitous energy substrates in splanchnic organs where fructolytic enzymes are expressed, and secondary delivery of these substrates to extrasplanchnic tissues. Fructose is a dispensable nutrient, yet its energy can be stored very efficiently owing to a rapid induction of intestinal fructose transporters and of splanchnic fructolytic and lipogenic enzymes by dietary fructose-containing caloric sweeteners. In addition, compared with fat or other dietary carbohydrates, fructose may be favored as an energy store because it uses different intestinal absorption mechanisms and different inter-organ trafficking pathways. These specific features make fructose an advantageous energy substrate in wild animals, mainly when consumed before periods of scarcity or high energy turnover such as migrations. These properties of fructose storage are also advantageous to humans who are involved in strenuous sport activities. In subjects with low physical activity, however, these same features of fructose metabolism may have the harmful effect of favoring energy overconsumption. Furthermore, a continuous exposure to high fructose intake associated with a low energy turnover leads to a chronic overproduction of intrahepatic trioses-phosphate production, which is secondarily responsible for the development of hepatic insulin resistance, intrahepatic fat accumulation, and increased blood triglyceride concentrations. In the long term, these effects may contribute to the development of metabolic and cardiovascular diseases.
Genomic imprinting, growth and maternal–fetal interactions
Authors: Cassidy Féaron C. , Charalambous Marika 
Published: March 2018

ABSTRACTIn the 1980s, mouse nuclear transplantation experiments revealed that both male and female parental genomes are required for successful development to term (McGrath and Solter, 1983; Surani and Barton, 1983). This non-equivalence of parental genomes is because imprinted genes are predominantly expressed from only one parental chromosome. Uniparental inheritance of these genomic regions causes paediatric growth disorders such as Beckwith–Wiedemann and Silver–Russell syndromes (reviewed in Peters, 2014). More than 100 imprinted genes have now been discovered and the functions of many of these genes have been assessed in murine models. The first such genes described were the fetal growth factor insulin-like growth factor 2 (Igf2) and its inhibitor Igf2 receptor (Igf2r) (DeChiara et al., 1991; Lau et al., 1994; Wang et al., 1994). Since then, it has emerged that most imprinted genes modulate fetal growth and resource acquisition in a variety of ways. First, imprinted genes are required for the development of a functional placenta, the organ that mediates the exchange of nutrients between mother and fetus. Second, these genes act in an embryo-autonomous manner to affect the growth rate and organogenesis. Finally, imprinted genes can signal the nutritional status between mother and fetus, and can modulate levels of maternal care. Importantly, many imprinted genes have been shown to affect postnatal growth and energy homeostasis. Given that abnormal birthweight correlates with adverse adult metabolic health, including obesity and cardiovascular disease, it is crucial to understand how the modulation of this dosage-sensitive, epigenetically regulated class of genes can contribute to fetal and postnatal growth, with implications for lifelong health and disease.
The performance of select universities of medical sciences based on the components affecting medical education
Authors: Tayebi Arasteh Mehdi , Pouragha Behrooz , Bagheri Kahkesh Masume 
Published: March 2018

Background: Every educational institution requires an evaluation system in order to find out about the quality and desirability of its activities, especially if it is a complex and dynamic environment. The present study was conducted to evaluate the educational performance of schools affiliated to Alborz University of Medical Sciences to help improve their performance. Methods: This descriptive analytical study was conducted in six schools affiliated to Alborz University of Medical Sciences in April 2016-October 2016 and October 2016-April 2017. The evaluation was carried out in two stages: self-assessment by service executives across schools, and external assessment in person by the university’s expert staff. The study tools included the components, criteria and desirable standards of educational performance in ten categories. Data were analyzed in SPSS. Results: The results obtained showed that, in April-October 2016, the highest performance evaluation scores pertained to the "secure testing" and "rules and regulations" components and the lowest to the "packages for reform and innovation in education" and "the school action plan" components. In October 2016-April 2017, the highest scores pertained to "workforce empowerment" and "secure testing" and the lowest to "faculty affairs" and "electronic education management system". Conclusions: Offering a balanced portrayal of the actual performance of schools using the right performance indicators in two consecutive periods can help further motivate the superior schools and encourage the weaker schools to strive harder. Competition among schools to get a higher score in the components affecting medical education helps mobilize them to move toward reform and improvement.
Lateral condylar fractures of the humerus in children
Authors: Ganeshalingam R. , Donnan A. , Evans O. , Hoq M. , Camp M. , Donnan L. 
Published: March 2018

Aims Displaced fractures of the lateral condyle of the humerus are frequently managed surgically with the aim of avoiding nonunion, malunion, disturbances of growth and later arthritis. The ideal method of fixation is however not known, and treatment varies between surgeons and hospitals. The aim of this study was to compare the outcome of two well-established forms of surgical treatment, Kirschner wire (K-wire) and screw fixation. Patients and Methods A retrospective cohort study of children who underwent surgical treatment for a fracture of the lateral condyle of the humerus between January 2005 and December 2014 at two centres was undertaken. Pre, intraoperative and postoperative characteristics were evaluated. A total of 336 children were included in the study. Their mean age at the time of injury was 5.8 years (0 to 15) with a male:female patient ratio of 3:2. A total of 243 (72%) had a Milch II fracture and the fracture was displaced by > 2 mm in 228 (68%). In all, 235 patients underwent K-wire fixation and 101 had screw fixation. Results There was a higher rate of nonunion with K-wire fixation (p = 0.02). There was no difference in Baumann’s angle, carrying angle or the rate of major complications between the two groups. No benefit was obtained by immobilizing the elbow for more than four weeks in either group. No short-term complications were seen when fixation crossed the lateral ossific nucleus. Conclusions Fixation of lateral condylar humeral fractures in children using either K-wires or screws gives satisfactory results. Proponents of both techniques may find justification of their methods in our data, but prospective, randomized trials with long-term follow-up are required to confirm the findings, which suggest a higher rate of nonunion with K-wire fixation. Cite this article: Bone Joint J 2018;100-B:387–95.