Miracle-dz/UniFAR-FTUs huggingface dataset:
Exercise-associated hyponatremia in Alaskan sled dogs: urinary and hormonal responses.

Exercise-associated hyponatremia occurs in horses and humans, both species that sweat, and in sled dogs, which do not sweat. To investigate the mechanism of exercise-associated hyponatremia in sled dogs, we measured water turnover, serum electrolyte concentrations and osmolality, plasma renal hormone concentrations, and urine composition of 12 fit Alaskan sled dogs before, during, and after a 490-km sled dog race (Ex group). Water turnover and serum electrolyte concentrations were measured in six similarly fit dogs that did not run (Sed group). Water turnover was significantly larger (P < 0.001) in Ex [190 +/- 19 (SD) ml . kg-1 . day-1] than in Sed dogs (51 +/- 13 ml . kg-1 . day-1). There were significant (P < 0.001) decreases in serum sodium concentration (from 148.6 +/- 2.8 to 139.7 +/- 1.9 mmol/l) and osmolality (from 306 +/- 9 to 296 +/- 5 mosmol/kgH2O) of Ex, but not Sed, dogs during the race. Plasma concentrations of arginine vasopressin decreased, whereas aldosterone and plasma renin activity increased significantly (P < 0. 01) during the race. Urine osmolality was unchanged, whereas urine sodium, potassium, and chloride concentrations decreased significantly (P < 0.05) and urine urea concentration increased (P = 0.06). These results demonstrate increased water turnover associated with hyponatremia and renal sodium conservation with maintained high urine osmolality in exercising Alaskan sled dogs.
Reduction in coronary microvascular resistance through cardiac resynchronization and its impact on chronic reverse remodelling of left ventricle in patients with non-ischaemic cardiomyopathy.

AIMS Left bundle branch block (LBBB) induces mechanical dyssynchrony, thereby compromising the coronary circulation in non-ischaemic cardiomyopathy. We sought to examine the effects of cardiac resynchronization therapy (CRT) on coronary flow dynamics and left ventricular (LV) function. METHODS AND RESULTS Twenty-two patients with non-ischaemic cardiomyopathy (New York Heart Association class, III or IV; LV ejection fraction, ≤35%; QRS duration, ≥130 ms) were enrolled. One week after implantation of the CRT device, coronary flow velocity and pressure in the left anterior descending coronary artery (LAD) and left circumflex coronary artery (LCx) were measured invasively, before and after inducing hyperemia by adenosine triphosphate administration, with two programming modes: sequential atrial and biventricular pacing (BiV) and atrial pacing in patients with LBBB or sequential atrial and right ventricular pacing in patients with complete atrioventricular block (Control). We assessed hyperemic microvascular resistance (HMR, mean distal pressure divided by hyperemic average peak velocity) and the relationship between the change in HMR and mid-term LV reverse remodelling. Hyperemic microvascular resistance was lower during BiV than during Control (LAD: 1.76 ± 0.47 vs. 1.54 ± 0.45, P < 0.001; LCx: 1.92 ± 0.42 vs. 1.73 ± 0.31, P = 0.003). The CRT-induced change in HMR of the LCx correlated with the percentage change in LV ejection fraction (R = -0.598, P = 0.011) and LV end-systolic volume (R = 0.609, P = 0.010) before and 6 months after CRT. CONCLUSION Cardiac resynchronization therapy improves coronary flow circulation by reducing microvascular resistance, which might be associated with LV reverse remodelling.
What works in citizenship and values education: attitudes of trainers towards the Itorero training program in post-genocide Rwanda

The article contributes to the existing literature on the civic and citizenship contextual framework. It investigates ways in which trainers appreciate Itorero , a non-formal citizenship and values education program for high school leavers (hereafter HSLs) in the post-genocide Rwanda. The article also establishes the best predictor of the success of Itorero program according to trainers’ perceptions. The research reported here used a survey questionnaire and interviews. The article shows that learners’ motivation and ideological background are significant factors for the success of citizenship and values education. It also highlights a contradiction between Itorero teaching and home-based socialization particularly in relation to the question of ethnicity. While the Itorero training teaches that Rwandans are ‘one people’, parents tell their children that Rwandans have three ethnic groups: Hutu, Tutsi and Twa. The article argues that there is a need to look for civic influences beyond the civics classroom and the school. Keywords: Citizenship and values education, Itorero , post-genocide Rwanda, trainers
Analysis of Mutational Lineage Trees from Sites of Primary and Secondary Ig Gene Diversification in Rabbits and Chickens1

Lineage trees of mutated rearranged Ig V region sequences in B lymphocyte clones often serve to qualitatively illustrate claims concerning the dynamics of affinity maturation. In this study, we use a novel method for analyzing lineage tree shapes, using terms from graph theory to quantify the differences between primary and secondary diversification in rabbits and chickens. In these species, Ig gene diversification starts with rearrangement of a single (in chicken) or a few (in rabbit) VH genes. Somatic hypermutation and gene conversion contribute to primary diversification in appendix of young rabbits or in bursa of Fabricius of embryonic and young chickens and to secondary diversification during immune responses in germinal centers (GCs). We find that, at least in rabbits, primary diversification appears to occur at a constant rate in the appendix, and the type of Ag-specific selection seen in splenic GCs is absent. This supports the view that a primary repertoire is being generated within the expanding clonally related B cells in appendix of young rabbits and emphasizes the important role that gut-associated lymphoid tissues may play in early development of mammalian immune repertoires. Additionally, the data indicate a higher rate of hypermutation in rabbit and chicken GCs, such that the balance between hypermutation and selection tends more toward mutation and less toward selection in rabbit and chicken compared with murine GCs.
Birth-related fatigue in 34-36-week preterm neonates: rapid recovery with very early kangaroo (skin-to-skin) care.

OBJECTIVE To test preterm neonates' physiologic and behavioral responses when placed skin-to-skin on their mother's chests, called kangaroo care (KC), for the first 6 hours after birth, instead of having the neonates go to an intensive care unit. DESIGN Convenience sampling was used in this descriptive study to enroll neonates who were given continuous KC beginning soon after birth in the delivery room and continuing for 6 hours. Heart rate, respiratory rate, oxygen saturation, abdominal temperature, and behavioral state were recorded each minute. SETTING Data were collected in the delivery room and in a private labor room in tropical Cali, Colombia. PARTICIPANTS Six 34-36-week preterm neonates with 5-minute APGAR scores of 6 or more were enrolled. Two neonates had grunting respirations before KC was begun. RESULTS Temperature rose rapidly to thermoneutral range. With few exceptions, heart rate, respiratory rate, and oxygen saturation remained within normal limits; grunting respirations in two neonates disappeared with warmed humidified oxygen and continuous KC. Sleep predominated, and neonates were discharged home by 48 hours being fully breastfed, suggesting that KC was an environment conducive to recovery from fatigue. CONCLUSIONS These data suggest that KC beginning in the delivery room can be given safely and perhaps with benefit to 34-36-week gestation neonates who appear healthy at birth. Kangaroo care was conducive to recovery from birth-related fatigue.
Bullying in Students with and Without Special Educational Needs

In the present study a concise presentation of the phenomenon of school bullying in students with and without special educational needs is attempted. Initially, a distinction is made between the terms “violence” and “school bullying”, the second term being a sub-category of the broader concept of violence. Then, some of the most important definitions which have been attributed to ‘‘school bullying’’ are presented. It is noted that there is no universally accepted definition, as the definition of such a complex and multidimensional phenomenon is not an easy task. Then, the main forms of school bullying are described as well as its principal causes are presented. Finally, international and national research data – principally from Greece - on the frequency of school bullying based on the type of disability/special educational needs is presented while suggestions are made for its confrontation.
Deleterious effects of acute treatment with a peroxisome proliferator-activated receptor-gamma activator in myocardial ischemia and reperfusion in pigs.

Thiazolidinediones exert electrophysiologic effects in noncardiac cells in vitro, but to date there have been no reports of effects on cardiac rhythm. We previously demonstrated that chronic pretreatment with a thiazolidinedione peroxisome proliferator-activated receptor (PPAR)-gamma activator, troglitazone, improves recovery of left ventricular (LV) function and substrate metabolism after ischemia and reperfusion, without causing arrhythmias. In this study, we determined whether similar salutary effects are achieved with acute treatment with troglitazone. Anesthetized pigs underwent 90 min of regional LV ischemia and 90 min of reperfusion. Fifteen pigs were treated with troglitazone (10 mg/kg load, 5 mg. kg(-1). h(-1) infusion i.v. ) beginning 1 h before ischemia. Seven pigs received corresponding vehicle. Plasma troglitazone concentration (mean 5 microg/ml) was similar to that achieved in clinical use of this agent. Before ischemia, acute troglitazone treatment had no effect on LV function, electrocardiogram, or substrate utilization. During ischemia or reperfusion, eight pigs in the troglitazone group died of ventricular fibrillation, compared with no pigs in the vehicle group (P < 0.05). Pigs that developed ventricular fibrillation had shorter QT intervals than survivors of either group. Among survivors, neither LV function nor substrate utilization differed between groups. Acute treatment with troglitazone increases susceptibility to ventricular fibrillation during myocardial ischemia and reperfusion. Whether thiazolidinediones have proarrhythmic potential in clinical use requires further investigation.
Mutations in the CDKN2A ( p16INK4a ) gene in microdissected sporadic primary melanomas

The role of the CDKN2A (p16INK4a) gene in sporadic primary melanomas has remained unclear due to the inadequate number of mutational studies. In the present study, we analyzed the entire coding region of the CDKN2A gene in microdissected sporadic primary melanomas, for the presence of mutations and polymorphisms, using 2 independent methods of mutation detection, SSCP and CMC. We found 11 intragenic mutations in 8 melanomas out of 31 (26%) and the majority of mutations were located in exon 1, with 2 cases harbouring multiple mutations. Of the mutations detected, 6 were C‐to‐T transitions, 4 involving CC sites; 2 melanomas showed a novel deletion of one of the two 24‐bp repeat units located at the 5′ end of exon 1. There was also a high frequency of C‐to‐G and C‐to‐T polymorphisms at the nucleotides 540 (frequency of G allele: 0.18) and 580 (frequency of T allele: 0.13) in the 3′ untranslated region. Int. J. Cancer 75:193–198, 1998. © 1998 Wiley‐Liss, Inc.
Primary and acquired pyrazinamide resistance in patients with pulmonary tuberculosis treated at a referral hospital in the city of Recife, Brazil.

OBJECTIVE To determine primary and acquired resistance to pyrazinamide in Mycobacterium tuberculosis strains isolated in sputum samples from patients with pulmonary tuberculosis. METHODS This was a prospective, descriptive study conducted between April and November of 2011 at a referral hospital for tuberculosis in the city of Recife, Brazil. Cultures, drug sensitivity tests, and tests of pyrazinamidase activity were conducted in a private laboratory in Recife. RESULTS Of the 71 patients included in the study, 37 were treatment-naïve and 34 represented cases of retreatment. Pyrazinamide-resistant strains were isolated in 14 (41.2%) of the 34 patients who had previously been treated for tuberculosis and in none of the 37 treatment-naïve patients. Of the 14 isolates, 10 (90.9%) tested negative for pyrazinamidase activity. A total of 60 isolates tested positive for pyrazinamidase activity. Of those, 56 (93.3%) were found to be sensitive to pyrazinamide. CONCLUSIONS The high frequency of pyrazinamide-resistant strains (41.2%) in patients previously treated for tuberculosis highlights the need for drug susceptibility testing prior to the adoption of a new treatment regimen.
Overwhelming post-splenectomy sepsis in patients with asplenia and hyposplenia: a retrospective cohort study

SUMMARY Overwhelming post-splenectomy infection (OPSI) is a serious complication of asplenia and is associated with encapsulated organisms, most commonly Streptococcus pneumoniae, but also Haemophilus influenzae and Neisseria meningitidis. We aimed to estimate the risk of infection in this patient group. We reviewed data collected by the Victorian Spleen Registry in Australia. On registration, all patients are asked about significant infections requiring admission to hospital for intravenous antibiotics; those requiring admission to ICU were defined as OPSI. In the 3274 asplenic patients registered 492 patients reported at least one episode of infection. There were 47 episodes of OPSI requiring intensive care (incidence rate 1·11/1000 patient-years). The risk of OPSI was highest in older patients, and there were no statistically significant differences in incidence by reason for splenectomy except for a higher rate in patients with medical hyposplenia. This study reinforces that post-splenectomy infection is a clinically significant but uncommon complication, and that fulminant infection requiring intensive care is a minority of all infections.
Nanoscale modification of chrysin for improved of therapeutic efficiency and cytotoxicity

Abstract Chrysin, as a flavone, is a promising drug candidate because of its multifaceted properties, such as anti-inflammatory, antioxidant and anticancer. However, its poor bioavailability is a bottleneck for pharmaceutical applications. To enhance the bioactive effects, chrysin-loaded poly (D,L-lactic-co-glycolic acid) and polyvinyl alcohol were successfully prepared to overcome problems associated with chrysin. The properties of modified nanochrysin were analysed by in vitro dissolution study, XRD, FTIR and SEM. Free radical scavenging potentials of the modified nanochrysin against DPPH were confirmed based on its stable antioxidant effects. A DNA instability enhancement was observed after H2O2 exposure, whereas chrysin decreased the H2O2 activity, and modified nanochrysin was more potent in this regard. Blood compatibility on red blood cells was confirmed by haemolytic and in vitro cytotoxicity assays. The in vitro anticancer activity of the modified nanochrysin towards MCF-7 and SKOV-3 cell lines using various parameters was investigated. The nanochrysin was found to exert cell growth arrest against both cancer cells in a dose-dependent manner. IC50 value was significantly decreased in nanochrysin in comparison with pure chrysin and induced apoptotic cell death pathway. The results of this study suggest that the nanochrysin might be used for medical applications and offer a beneficial formulation for chemotherapy.
The mammary ducts create a favourable microenvironment for xenografting of luminal and molecular apocrine breast tumours

There is a paucity of models for hormone receptor‐positive (HR+) breast cancer because of the difficulty of establishing xenografts from these tumours. We show that this obstacle can be overcome by injecting human tumour cells directly into the mammary ducts of immunodeficient mice. Tumours from 31 patients were infected overnight with a lentiviral vector expressing tdTomato and injected through the nipple into the mammary ducts of NOD‐SCID‐IL2RG−/− mice. Tumours formed in the mice in 77% of cases after the first injection (6/8 luminal A, 15/20 luminal B, and 3/3 molecular apocrine). Four luminal A and one molecular apocrine graft were tested in secondary and tertiary grafts: all were successfully passaged in secondary and 4/5 in tertiary grafts. None of the samples engrafted when injected subcutaneously. The morphology, oestrogen receptor (ER), progesterone receptor (PR), androgen receptor (AR), and Ki‐67 profiles of the clinical samples were maintained in the tertiary grafts. We also show that the intraductal approach can be used to test the response to targeted therapy with fulvestrant and palbociclib, using a genetically defined ER+ model. We conclude that the mammary ducts create a microenvironment that is uniquely favourable to the survival and growth of tumours derived from mammary hormone‐sensing cells. This approach opens the door to testing genomically targeted treatment of HR+ tumours in precision medicine programmes. Copyright © 2016 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
A Comparative Study of the Effects of Intravitreal Anidulafungin, Voriconazole, and Amphotericin B in an Experimental Candida Endophthalmitis Model

ABSTRACT Purpose: To compare the safety and efficacy of intravitreal anidulafungin injection with voriconazole and amphotericin B (Amp B) in an experimental Candida endophthalmitis (CE) model. Methods: Intravitreal 1 × 105 CFU/0.1 ml Candida albicans was injected into the right eyes of 24 New Zealand rabbits, which were divided into 4 groups. Voriconazole 50 μg/0.1 ml, Amp B 10 μg/0.1 ml, and Anidulafungin 50 μg/0.1 ml were injected by intravitreal injection 72 h after inoculation. The control group was injected with 0.1 ml 0.9% NaCl. Clinical scoring was performed by assessing the cornea, conjunctiva, iris, and vitreous on days 3 and 7 of therapy. At the end of the study, the right eyes of all rabbits were enucleated and histopathological evaluation was performed. Therapy groups were compared according to the clinical, histopathological, and microbiological analysis scores. Results: Total clinical scores were significantly different between treatment groups and the control group (p < 0.05). On day 7 of the therapy, clinical scores of the anidulafungin group were found to be significantly lower when compared with the other therapy groups, while a significant improvement was observed in the eyes of rabbits in the anidulafungin group (p < 0.05). Also, microbiological scores of the anidulafungin group were lower than those of the control group (p < 0.05). Histopathological scores of the anidulafungin treatment group were significantly better than the voriconazole and control groups. Inflammation was evidently suppressed and marked retinal toxicity was not observed with anidulafungin. Conclusions: This is the first study comparing the efficacy of anidulafungin with other antifungal agents. In this CE model, an intravitreal single dose of anidulafungin was shown to be noninferior to voriconazole and Amp B. As an alternative to Amp B or voriconazole, intravitreal anidulafungin is suggested as an effective antifungal agent for the treatment of CE.
Possible morphological substrates for GABA‐mediated presynaptic inhibition in the lamprey spinal cord

Gamma‐aminobutyric acid (GABA) neurons intrinsic to the lamprey spinal cord are known to modulate synaptic transmission from interneurons active during locomotion and from mechanosensory dorsal cells. Many of these physiological effects are presynaptic. To establish the morphological substrates for these axo‐axonic interactions, an ultrastructural analysis was performed with an antiserum to fixed GABA. The GABA immunoreactivity (ir) was detected by postembedding peroxidase‐antiperoxidase and immunogold techniques. GABA‐ir terminals were found to make appositions with unlabelled axons located in the dorsal columns and in the ventrolateral aspect of the spinal cord. In the ventrolateral part of the cord, similar appositions between different GABA‐ir terminals were also observed. The immunolabelled terminals contained spherical to pleomorphic synaptic vesicles, and also glycogen granules and dense core vesicles. In some cases, the fine structure of the contacts between immunogold‐labelled terminals and unlabelled axons suggested a synaptic relationship. Such a relation was found in a relatively small proportion (2–3%) of the appositions studied. These specializations were always observed in close relation to an output synapse of the postsynaptic axon. It is suggested that the axo‐axonal contacts described may provide an effective modulation of the synaptic transmission from axons in the lamprey spinal cord. © 1993 Wiley‐Liss, Inc.
d‐α‐tocopheryl polyethylene glycol 1000 succinate‐containing vehicles provide no detectable chemoprotection from oxidative damage

The objective of this study was to evaluate potential protective effects of vehicles containing d‐α‐tocopheryl polyethylene glycol 1000 succinate (TPGS), which may impact nonclinical safety assessments of oxidative processes. This was achieved by evaluating plasma, liver and adrenal gland concentrations of d‐α‐tocopheryl succinate (TS) and d‐α‐tocopherol as well as oxidative status of plasma following oral dosing of TPGS‐containing vehicles, intraperitoneal (IP) dosing of TS or ex vivo treatment of blood with H2O2. Male and female rats were dosed orally with formulations containing 5% or 40% TPGS (70 or 550 mg kg–1 day–1 TS, respectively) for 1 week. A control group was dosed orally with polyethylene glycol‐400 (PEG‐400; no vitamin E) and positive control animals received a single 100 mg kg–1 day–1 IP injection of TS. Whole blood from untreated animals was treated ex vivo with 5 or 50 mm H2O2, with or without TS (0.5, 5, 50 or 500 μm) or ascorbate (1 mm), for 1 h. Oral TPGS treatments did not affect d‐α‐tocopherol concentrations in plasma or adrenal glands and caused only transient increases in liver. Concentrations of TS in plasma, liver and adrenal glands were undetectable in control animals, but increased in all other groups. Oral administration of TPGS did not reduce plasma lipid peroxidation in vivo. Substantially greater TS concentrations used ex vivo (100× greater than in vivo) were also unable to reduce lipid peroxidation in H2O2‐treated whole blood. These results provide evidence that administration of oral TPGS vehicles is unlikely to impact nonclinical safety assessments of pharmaceuticals. Copyright © 2014 John Wiley & Sons, Ltd.