bluuebunny/crossref_metadata_2025_split huggingface dataset:
Assessment of Bleeding for the Evaluation of Therapeutic Preparations in Small Animal Models of Antibody-Induced Hemophilia and von Willebrand Disease
Authors: Turecek P L , Gritsch H , Richter G , Auer W , Pichler L , Schwarz H P 
Published: July 2018

SummaryThree small animal models of bleeding are described and used to evaluate the effects of preparations intended for therapy of human bleeding disorders. We modified techniques for the assessment of bleeding to be able to reproducibly quantify blood loss and rate of blood flow in addition to the measurement of bleeding time.Temporary hemophilia was induced in a rabbit model by injection of high titer human inhibitor plasma [>1000 Bethesda units (BU)/ml]. A decrease in rabbit FVIII from normal values to below the limit of detection was observed within 30 min, cuticle bleeding time changed from normal (approx. 10 min) to steady state bleeding (>30 min), and the rate of blood flow increased from 4 to >30 µl blood/min. Infusion of an activated prothrombin complex concentrate (FEIBA STIM4, Immuno) at doses between 75 and 150 U/kg normalized the rate of blood flow, while infusion of FVIII/vWF concentrate resulted in partial correction. Administration of FVIIa, both recombinant and plasma-derived, failed to correct bleeding, however. In an analogous murine model, FVIII/ vWF inhibitor plasma was obtained by immunizing goats with a purified human FVIII/vWF complex. This plasma cross-reacted with mouse vWF in vitro. Injection of the anti-FVIII/vWF inhibitor plasma into mice caused a decrease in vWF antigen, in some animals with a complete loss of vWF multimers comparable to severe von Willebrand disease. A specific anti-vWF inhibitor plasma obtained by immunization of goats with recombinant vWF was used in a further murine model, resulting in a gradual but substantial decrease in FVIII as well as in intensive bleeding. The infusion of a FVIII/vWF concentrate (IMMUNATE, IMMUNO) normalized the rate of blood flow in both murine models. The same assessment methods were used to characterize bleeding in a natural mouse model of von Willebrand disease (strain RIIIS/J). The use of quantitative techniques of assessment of blood loss and rate of blood flow appears to be a helpful tool for characterizing hemorrhagic situations and evaluating the capacity of therapeutic preparations to correct hemostatic defects.
Streptokinase Entrapment in Interdigitation-Fusion Liposomes Improves Thrombolysis in an Experimental Rabbit Model
Authors: Perkins W R , Vaughan D E , Plavin S R , Daley W L , Rauch J , Lee L , Janoff A S 
Published: July 2018

SummaryThe successful design of new thrombolytic agents depends on providing these agents with increased clot selectivity. As recently demonstrated (10), entrapment of tissue plasminogen activator into liposomes apparently provided the selective targeting needed to improve the efficacy of this fibrinolytic agent. To test whether liposomal entrapment would benefit streptokinase, a fibrinolytic agent with a different mode of action and inactivation, we compared liposomal streptokinase with free streptokinase in an experimental rabbit model of thrombolysis.First we adapted a new method to produce liposomes of high entrapment efficiency, termed interdigitation-fusion (IF) liposomes, for the encapsulation of streptokinase. This system was then tested in an in vivo rabbit model of thrombolysis where animals with established clots were infused with either free streptokinase (40,000 U/kg), liposomally entrapped streptokinase, free streptokinase + empty liposomes, or the corresponding amount of empty liposomes or saline. Significant differences (p <0.05) in the percent clot lysis were observed between saline control (22.4 ± 3.3%; mean ± S.E.), free streptokinase (36.3 ± 3.4%), and liposomal streptokinase (47.4 ± 1.4%). Importantly, animals treated with empty liposomes experienced a level of thrombolysis (32.4 ± 2.8%) not different to that produced by free streptokinase or empty liposomes plus free streptokinase (38.0 ± 2.0%). We believe the effect of liposomes alone is due to a transient redistribution or margination of circulating platelets.When tested in rabbits immunized against streptokinase, liposomal (33.8 ± 1.5%) but not free streptokinase (29.3 ± 2.1%) showed significant thrombolytic activity compared to saline (22.4 ± 3.3%) (p <0.05). The thrombolytic activity was comparable to free streptokinase in nonimmunized rabbits. This suggests liposomal streptokinase would have better thrombolytic activity than streptokinase alone and still provide to those patients possessing high levels of anti-streptokinase antibodies (5% of the population) the equivalent degree of therapy expected from free streptokinase.
The Leu33/Pro Polymorphism (PIA1/PIA2
) of the Glycoprotein IIIa (GPIIIa) Receptor Is Not Related to Myocardial Infarction in the ECTIM Study
Authors: Herrmann Stefan-Martin , Poirier Odette , Marques-Vidal Pedro , Evans Alun , Arveiler Dominique , Luc Gerald , Emmerich Joseph , Cambien François 
Published: July 2018

SummaryThe GPIIb/IIIa receptor complex may contribute to acute coronary syndromes by mediating platelet aggregation. The Leu33/Pro polymorphism (PlAl/PlA2) of the GPIIIa has recently been shown to be associated with CHD in a small case-control study. We have investigated this polymorphism in a large multicenter study of patients with myocardial infarction and controls and found no difference in the distribution of allele and genotype frequencies between cases and controls.
Platelet Shape Change and Cytoskeletal Assembly: Effects of pH and Monovalent Cation lonophores
Authors: Leven R M , Gonnella P A , Reeber M J , Nachmias V T 
Published: July 2018

SummaryThe monovalent cation ionophores monensin and nigericin cause platelet shape change at a rate of approximately 1/20 of that caused by ADP. The effect of monensin was studied further. Shape change caused by monensin is pH dependent, increasing in rate as extracellular pH increases. Monensin induced shape change is not blocked by 30 μM cinanserin which completely inhibits serotonin induced shape change. Also, the amount of serotonin secreted by monensin treated platelets is below the threshold required to induce shape change. 100 μM ATP which inhibits ADP induced shape change does not affect monensin induced shape change. Amiloride, a sodium transport blocker, inhibits both the rate of ADP induced shape change and platelet spreading on poly-lysine coated glass. Amorphous platelet cyto-skeletons isolated from resting platelets at pH 6.8 with Mg+ + but not Ca++ can be transformed into filament bundles by subsequent incubation at pH 7.6. We conclude that platelet shape change is at least in part triggered by changes in cellular Na+ and pH
Abnormal Properties and Behaviors of Antithrombin III Found in a Thrombophilic Patient: Defective Biological Functions and Dissimilar Antigenic Determinants
Authors: Murayama Hideki , Matsuda Michio 
Published: July 2018

SummaryAbnormal properties of antithrombin III have been found in a 55-year-old male who has been thrombophilic over the last seven years. They are characterized by 1) defective inhibition of thrombin and activated blood coagulation factor X, 2) reduced affinity to heparin and 3) partial immunological identity with the normal molecule. The antithrombin III molecule, however, preserves a single-chain structure and an apparently identical molecular weight with that of the normal molecule. It is, thus, very unlikely that the impaired functions of antithrombin III in the patient’s plasma are induced by possible proteolytic modifications of the molecule by thrombin or other related activated blood coagulation factors.Since no other members of his immediate family have been found to be affected, the abnormality may be acquired rather than genetically determined, although further investigation is necessary for the elucidation of the abnormality of the molecule.
Pilotstudie: Mikrobiom und Darmbarriere bei Anorexia nervosa
Authors: Mörkl Sabrina , Lackner Sonja , Meinitzer Andreas , Gorkiewicz Gregor , Kashofer Karl , Painold Annamaria , Holl Anna , Holasek Sandra 
Published: July 2018

Zusammenfassung
Einleitung Forschungsergebnisse zeigen Veränderungen des Darmmikrobioms bei Anorexia nervosa (AN). Die Alpha-Diversität (AD) repräsentiert die Anzahl von Bakterienarten im Darm. Eine verminderte AD und erhöhte Darmpermeabilität (Zonulin) kann zu Inflammation und Veränderungen der Nährstoffaufnahme führen. Methoden AD wurde aus Stuhlproben von 18 AN-Patientinnen sowie 20 normalgewichtigen Kontrollen (NK) nach 16S RNA Sequenzierung ermittelt. Zusätzlich wurden Zonulin als Marker der Darmbarriere und inflammatorische Parameter bestimmtErgebnisse AN-Patientinnen wiesen im Vergleich zu NK eine verminderte AD auf (Chao-1-Diversity: p=0.043, number of observed species p=0.042). Zonulin zeigte sich bei AN-Patientinnen im Vergleich zu NK nicht signifikant vermindert. Es gab keine Korrelationen zwischen den Serumparametern und AD. Diskussion AN-Patientinnen weisen unabhängig von der Darmpermeabilität eine erniedrigte AD auf. Die reduzierte AD kann die Kalorienaufnahme bei AN zusätzlich negativ beeinflussen. Diese Ergebnisse tragen zu einem besseren Krankheitsverständnis und der Entwicklung neuer Therapieoptionen bei.
Ancient Stoicism and modern life
Authors: Inwood Brad 
Published: July 2018

Abstract
In the ancient world of the Greeks and Romans, the idea of philosophy as a way of life had its fullest and clearest development in Stoicism. ‘Ancient Stoicism and modern life’ provides an overview of Stoicism’s major figures. The Stoic school was founded by Zeno in the late 4th century bce. His students, Cleanthes and Aristo, developed different interpretations of Stoic philosophy—Large Stoicism and Minimal Stoicism, respectively. However, it is the work of much later writers—Seneca, Epictetus, and Marcus Aurelius—that is accessible today. The application of Stoicism to modern life by French philosopher Pierre Hadot and American fighter pilot James Stockdale is also considered.
Reading Stoics today
Authors: Inwood Brad 
Published: July 2018

Abstract
For modern readers, despite not being typical representatives of the school, Epictetus and Marcus Aurelius are the foundation for our understanding of Stoicism for two reasons. First, except for Seneca, theirs are the earliest and almost only complete works we have from the ancient Stoics. Second, both Epictetus and Marcus are atypical in the way they wrote and the kind of audience they chose to address. ‘Reading Stoics today’ considers why Seneca is not more important in our contemporary popular understanding of Stoicism. How did the Stoic whose legacy was of such basic importance in the later middle ages and Renaissance come to take a back seat in general culture?
The origins of the school
Authors: Inwood Brad 
Published: July 2018

Abstract
The earliest Stoics shared a great deal with Plato and his followers, so why didn’t the early Stoics just join Plato’s Academy? The problem was metaphysics. Plato’s most distinctive doctrine was his theory of Forms, but in the view of Aristotle and the Stoics, Platonic Forms cannot be distinct and separate substances that cause physical particulars to be what they are. ‘The origins of the school’ explains that the Stoics had to develop a metaphysical status for such things that acknowledged their ‘reality’ without treating them as bodies. It explains the Stoics’ nominalism and how Stoics adopted the division of philosophy into logic, physics, and ethics.
Physics
Authors: Inwood Brad 
Published: July 2018

Abstract
One of the main dividing lines in Greek physical theory was the question of the nature of matter. ‘Physics’ explains that the Stoics fit squarely into the non-atomistic tradition, being definitely committed to the infinite divisibility of matter, the rejection of void, and the fundamental role of four basic forms of matter—earth, air, fire, and water—with no need for a special kind of stuff for the heavenly bodies. It considers the ‘big picture’ of Stoic cosmology and their providential determinism. If the determined world is part of a grand plan aimed at producing the good, why is there so much bad in the world?
Logic
Authors: Inwood Brad 
Published: July 2018

Abstract
‘Logic’ explains that logic has a broad and a narrow sense in Stoic theory and deals with a subset of sayables and meanings. Their logic is close to what we would call propositional logic. Chrysippus was the pioneer and genius of Stoic logic. He seems to have held that in simple assertoric logic all valid inference forms could be reduced to combinations of five basic and indemonstrable argument forms, with the assistance of several other logical and metalogical principles. The Stoics also worked extensively on modal syllogistic and other areas of research in logic with a sophistication not paralleled in some cases until the 20th century.
Auditory Training Reverses Lead (Pb)-Toxicity-Induced Changes in Sound-Azimuth Selectivity of Cortical Neurons
Authors: Liu Xia , Wei Fanfan , Cheng Yuan , Zhang Yifan , Jia Guoqiang , Zhou Jie , Zhu Min , Shan Ye , Sun Xinde , Yu Liping , Merzenich Michael M , Lurie Diana I , Zheng Qingyin , Zhou Xiaoming 
Published: July 2018

Abstract
Lead (Pb) causes significant adverse effects on the developing brain, resulting in cognitive and learning disabilities in children. The process by which lead produces these negative changes is largely unknown. The fact that children with these syndromes also show deficits in central auditory processing, however, indicates a speculative but disturbing relationship between lead-exposure, impaired auditory processing, and behavioral dysfunction. Here we studied in rats the changes in cortical spatial tuning impacted by early lead-exposure and their potential restoration to normal by auditory training. We found animals that were exposed to lead early in life displayed significant behavioral impairments compared with naïve controls while conducting the sound-azimuth discrimination task. Lead-exposure also degraded the sound-azimuth selectivity of neurons in the primary auditory cortex. Subsequent sound-azimuth discrimination training, however, restored to nearly normal the lead-degraded cortical azimuth selectivity. This reversal of cortical spatial fidelity was paralleled by changes in cortical expression of certain excitatory and inhibitory neurotransmitter receptor subunits. These results in a rodent model demonstrate the persisting neurotoxic effects of early lead-exposure on behavioral and cortical neuronal processing of spatial information of sound. They also indicate that attention-demanding auditory training may remediate lead-induced cortical neurological deficits even after these deficits have occurred.
Improved Bounds for Restricted Families of Projections to Planes in ℝ3
Authors: Orponen Tuomas , Venieri Laura 
Published: July 2018

Abstract
For $e \in S^{2}$, the unit sphere in $\mathbb{R}^3$, let $\pi _{e}$ be the orthogonal projection to $e^{\perp } \subset \mathbb{R}^{3}$, and let $W \subset \mathbb{R}^{3}$ be any $2$-plane, which is not a subspace. We prove that if $K \subset \mathbb{R}^{3}$ is a Borel set with $\dim _{\textrm{H}} K \leq \tfrac{3}{2}$, then $\dim _{\textrm{H}} \pi _{e}(K) = \dim _{\textrm{H}} K$ for $\mathcal{H}^{1}$ almost every $e \in S^{2} \cap W$, where $\mathcal{H}^{1}$ denotes the one-dimensional Hausdorff measure and $\dim _{\textrm{H}}$ the Hausdorff dimension. This was known earlier, due to Järvenpää, Järvenpää, Ledrappier, and Leikas, for Borel sets $K$ with $\dim _{\textrm{H}} K \leq 1$. We also prove a partial result for sets with dimension exceeding $3/2$, improving earlier bounds by D. Oberlin and R. Oberlin.
A Typology of Breastfeeding Mothers of Preterm Infants
Authors: Niela-Vilén Hannakaisa , Axelin Anna , Salanterä Sanna , Melender Hanna-Leena 
Published: July 2018

Background:
Breastfeeding is an important element of motherhood with a preterm infant, but the role of maternal emotions in relation to breastfeeding is vague.

Purpose:
To describe maternal emotions regarding and insights into breastfeeding during the first year after a preterm birth.

Methods:
In total, 80 mothers of preterm infants (<35 gestational weeks) participated in this secondary analysis of a larger study. The data were collected with an open question at discharge and 3, 6, and 12 months after the expected birth date and analyzed using thematic analysis.

Findings:
A typology of breastfeeding mothers of preterm infants was created. The group of survivors wished to be breastfeeding mothers, but after some unexpected difficulties, they had to give up their dream. The disappointment alleviated with time, but some of the mothers still harbored self-accusations after a year. The highfliers were mothers who succeeded in breastfeeding because of their own persistence. They described breastfeeding as enjoyable for both the mother and the infant. The pragmatist mothers breastfed because it was the general norm and a practical way to feed the infant; breastfeeding caused neither passion nor discomfort. The group of bottle-feeding–oriented mothers expressed that breastfeeding did not interest them at any point.

Implications for Practice:
Being aware of the typology could help nurses and midwives carefully observe mothers' individual counselling needs. Mothers' wishes and decisions regarding breastfeeding need to be respected and supported without any judgment.

Implications for Research:
The possibilities to tailor breastfeeding interventions based on the typology should be investigated.
A Qualitative Study on Factors Modulating Tinnitus Experience
Authors: Colagrosso Emilia M. G. , Fournier Philippe , Fitzpatrick Elizabeth M. , Hébert Sylvie 
Published: July 2018

Objectives:
It is well recognized that tinnitus can severely interfere with important aspects of life such as sleep, concentration abilities, social activities, and mood. However, the impact of tinnitus may vary greatly from one individual to another, with some being severely affected and others only experiencing a slight handicap. Information from participants’ experiences with tinnitus could help explain such variability. The full experience of living with tinnitus from a patient’s perspective has been under-investigated, especially in comparison with the large and extensive body of qualitative research on hearing loss. This study aims to contribute to fill this gap and assess participants’ experience of living with tinnitus.

Design:
As part of a larger mixed design study, this inquiry used qualitative analyses to investigate participant’s experiences with tinnitus. Twenty-seven tinnitus participants of different ages, sexes, audiometric profiles, and tinnitus severities were invited to discuss their tinnitus through semistructured interviews and journal entries. The interviews took place 1 month after participants completed a 3-week trial period with tinnitus maskers.

Results:
The findings were grouped into three main themes: participants’ appraisal of their tinnitus, factors modulating tinnitus experience, and consequences of tinnitus. Regarding participants’ appraisal of their tinnitus, a dissociation between the tinnitus sensation (pitch, loudness) and tinnitus experience (annoyance/distress) was reported. Factors modulating tinnitus experience were classified as environmental factors and individual-specific factors, which were further divided into soundscape and other environmental factors for the former and attentional focus, stress level, physical state, fatigue, and auditory effort for the latter. Consequences of tinnitus included distraction, disrupted mental health and mood, headaches, fatigue, sleep disturbances, hearing difficulties, disrupted social life, and frustration.

Conclusions:
Two of the main themes (participants’ appraisal of their tinnitus and consequences of tinnitus) were consistent with findings from a few previous qualitative studies. Factors modulating tinnitus experience also emerged as a prominent theme. Indeed, participants described a plethora of factors that affected their experiences of tinnitus. On the basis of these findings, an attentional model is proposed to account for how these factors might modulate the effects of tinnitus.
INCIDENCE OF LATE AGE-RELATED MACULAR DEGENERATION IN EYES WITH RETICULAR PSEUDODRUSEN
Authors: Kong Mingui , Kim Sungmin , Ham Don-Il 
Published: July 2018

Purpose:
To investigate the incidence of late age-related macular degeneration (AMD) over 3 years and risk factors for the development of late AMD in Korean patients having reticular pseudodrusen (RPD).

Methods:
Clinical records of Korean RPD patients with no late AMD at first examination and completion of 3 years of regular follow-up were retrospectively reviewed. All patients underwent complete ocular examinations, including multimodal imaging. Reticular pseudodrusen were classified as a separate lesion different from other early AMD lesions, and RPD were not considered a sign of early AMD. Risk factors for the development of late AMD were assessed.

Results:
One hundred and ninety-two RPD eyes of 104 patients were included in this study. Mean age of patients was 69.4 ± 8.9 years, and other early AMD lesions were accompanied in 152 eyes (79.2%) at baseline. During 3 years, late AMD occurred in 30 eyes (15.6%); geographic atrophy in 24 eyes (12.5%); and neovascular AMD in 6 eyes (3.1%). Eyes having early AMD at baseline revealed significantly higher incidence for late AMD than those eyes having no early AMD at baseline (18.4% vs. 5%, P = 0.048). Late AMD occurred in 5 eyes (38.5%) from 13 fellow RPD eyes of unilateral late AMD at baseline. In logistic regression analysis, thin choroidal thickness, diffuse distribution of RPD, and the presence of late AMD on fellow eye at baseline were significant risk factors for developing late AMD in RPD eyes.

Conclusion:
Reticular pseudodrusen eyes revealed various progression rates to late AMD according to AMD status of both eyes. More frequent monitoring should be considered for patients with RPD at risk of progression to late AMD.
LINEZOLID-INDUCED MITOCHONDRIAL TOXICITY PRESENTING AS RETINAL NERVE FIBER LAYER MICROCYSTS AND OPTIC AND PERIPHERAL NEUROPATHY IN A PATIENT WITH CHRONIC GRANULOMATOUS DISEASE
Authors: Pilania Rakesh K. , Arora Atul , Agarwal Aniruddha , Jindal Ankur K. , Aggarwal Kanika , Krishnan Gopala , Suri Deepti , Gupta Anju , Singh Surjit , Gupta Vishali 
Published: July 2018

Purpose:
To report a case with unique changes in the retinal nerve fiber layer observed on optical coherence tomography in a 22-year-old patient on chronic linezolid therapy for recurrent pyogenic liver abscesses with underlying chronic granulomatous disease.

Methods:
History and clinical examination, laboratory evaluation, fluorescein angiography, and optical coherence tomography.

Results:
The patient presented with best-corrected visual acuity of 20/200 in the right eye and 20/125 in the left eye. He had moderate optic disk edema and superotemporal field defects bilaterally. Swept-source optical coherence tomography revealed the presence of retinal nerve fiber layer microcystic spaces. Laboratory tests showed no positive findings except for an elevated lactic acid level. Linezolid-induced optic neuropathy was suspected, and the drug was discontinued. Six weeks after termination of oral linezolid therapy, the optic disk edema and the microcystic spaces in the retinal nerve fiber layer resolved, and the best-corrected visual acuity improved to 20/50 in the right and 20/40 in the left eye, respectively.

Conclusion:
Linezolid is a widely used antibiotic with broad-spectrum action. However, chronic use can lead to mitochondrial toxicity that may have protean manifestations. Ocular examination, particularly of the optic nerve and nerve fiber layer using multimodal imaging, is critical in diagnosing such toxicity.