Miracle-dz/UniFAR-FTUs huggingface dataset:
VO2 slow component correlates with vastus lateralis de-oxygenation and blood lactate accumulation during running.

BACKGROUND In the present study, vastus lateralis de-oxygenation was monitored contemporarily with VO2 changes along a severe constant intensity running exercise, after the 3rd min up to volitional exhaustion. Blood lactate accumulation was also measured before, during and after running. METHODS Eleven male amateur soccer players volunteered for the study. Subjects mean age, height, and body weight were 22.9+/-2 yrs, 177.5+/-6.2 cm, 71.7+/-4 kg, respectively. Measurements were carried out during running on a treadmill. Ventilatory and gas exchange parameters were measured at the mouth on a breath-by-breath basis. For blood lactate concentration accumulation measurement, capillary blood samples were taken from the fingertip. The oxygenation of the vastus lateralis muscle were measured by a continuous wave NIRS portable instrument. By means of two pretests the onset of [La]b accumulation and its associated velocity (vOBLA), and the peak of oxygen uptake and its associated velocity (vVO2,peak) were assessed. The test consisted of running on the treadmill up to volitional exhaustion at a constant velocity corresponding to vOBLA plus 50% of the difference between vVO2,peak and vOBLA (v50%Delta). RESULTS The principal finding of this study was that vastus lateralis de-oxygenation changes measured during running correlate with a) oxygen uptake changes between the 3rd min of exercise and the time corresponding to the subject's volitional exhaustion; b) blood lactate concentration increments measured at the 3rd and the 6th min of exercise and at the time corresponding to the subject's volitional exhaustion. CONCLUSIONS In conclusion, the results of the present study support our hypothesis that the vastus lateralis de-oxygenation contributes consistently to the VO2 slow component development in running.
Cyclosporin a induces in vivo inhibition of resorption and stimulation of formation in rat bone

We investigated a possible “in vivo” effect of cyclosporin A, an immunosuppressive agent, on normal rat bone remodeling. At an oral daily dose of 7 mg/kg for 14 days, the blood level of cyclosporin A was in the usual effective range and no change in renal function or magnesium metabolism was observed. Treated rats had decreased bone resorption: urinary hydroxyproline, plasma acid phosphatase, and the number of osteoclasts in caudal vertebrae were significantly reduced. By contrast, bone formation assessed by dynamic histomorphometry after double tetracycline labeling was increased. No modification of calciotropic hormones (vitamin D metabolites and parathyroid hormone as assessed by urinary cyclic AMP) was observed at the end of the treatment. These results suggest that in vivo cyclosporin A treatment induces bone remodeling modifications related to either a direct or a lymphokine‐mediated effect on bone cells.
Regeneration into the Spinal Cord of Transected Dorsal Root Axons Is Promoted by Ensheathing Glia Transplants

The permissivity of adult olfactory bulb to the ingrowth of olfactory axons could be due to the unique properties of ensheathing glia. To test whether these glial cells could be used to promote axonal regeneration in a spontaneously nonregenerating system, we transplanted suspensions of pure ensheathing cells into a rhizotomized spinal cord segment. Ensheathing cells were purified away from other cell types by immunoaffinity, using anti-p75 nerve growth factor receptor. After laminectomy at the lower thoracic level, the spinal cord was exposed and one dorsal root (T10) was completely transected at the cord entry point. The root stump was microsurgically anastomosed to the cord and a suspension of ensheathing cells was transplanted in the spinal cord at the dorsal root entry zone. Three weeks after transplantation, numerous regenerating dorsal root axons were observed reentering the spinal cord. Ingrowth of dorsal root axons was observed using DiI and antibodies against calcitonin gene-related peptide and growth-associated protein. Primary sensory afferents invaded laminae 1, 2, and 3, grew through laminae 4 and 5, and reached the dorsal grey commissure and lamina 4 of the contralateral side. We did not observe regenerating axons within the ipsilateral ventral horn and dorsal column. Transplanted ensheathing cells reached the same laminae as axons. Neither ensheathing cells nor regenerating axons invaded those laminae they did not innervate under normal circumstances. In conclusion, the regeneration of injured dorsal root axons into the adult spinal cord was possible after ensheathing glia transplantation. The use of ensheathing cells as stimulators of axonal growth might be generalized to other central nervous system injuries.
Nurses’ self-efficacy, rather than their knowledge, is associated with their engagement in advance care planning in nursing homes: A survey study

Background: Considering social cognitive theory and current literature about successful advance care planning in nursing homes, sufficient knowledge and self-efficacy are important preconditions for staff to be able to carry out advance care planning in practice. Aim: Exploring to what extent nurses’ knowledge about and self-efficacy is associated with their engagement in advance care planning in nursing homes. Design: Survey study as part of a baseline measurement of a randomised controlled cluster trial (NCT03521206). Setting/participants: Nurses in a purposive sample of 14 nursing homes in Belgium. Methods: A survey was distributed among nurses, evaluating knowledge (11 true/false items), self-efficacy (12 roles and tasks on 10-point Likert-type scale) and six advance care planning practices (yes/no), ranging from performing advance care planning conversations to completing advance directives. Results: A total of 196 nurses participated (66% response rate). While knowledge was not significantly associated with advance care planning practices, self-efficacy was. One unit’s increase in self-efficacy was statistically associated with an estimated 32% increase in the number of practices having carried out. Conclusions: Nurses’ engagement in advance care planning practices is mainly associated with their self-efficacy rather than their knowledge. Further research is necessary to improve the evidence regarding the causal relationship between constructs. However, these results suggest that educational programmes that focus solely on knowledge might not lead to increasing uptake of advance care planning in nurses.
Effect of acute stressors on endocrinological and immunological functions in lambs.

Lambs were used to evaluate the effect of acute heat stress (HS) or restraint and isolation stress (RIS) on endocrinological and immunological functions. In Exp. 1, lambs were exposed to HS (35 degrees C) and control lambs (CN) were exposed to 21 degrees C for 24 h in two replicates (n = 8 lambs total per treatment). Samples of serum were obtained at frequent intervals for evaluation of cortisol; whole blood was obtained for total and differential leukocyte numbers and lymphocyte blastogenic function. The time-trends for cortisol between HS and CN lambs were different following treatment (P less than .005), but neither leukocyte numbers nor lymphocyte blastogenesis in response to mitogens were affected by acute exposure to the elevated ambient temperature. In Exp. 2, lambs (n = 6 per treatment) were given a 6-h RIS treatment and control lambs remained in their home stanchions (CON). Plasma and serum were obtained frequently during treatment and continued until 24 h after the onset of treatment. Plasma was evaluated for adrenocorticotropic hormone (ACTH) and serum was assayed for cortisol. Samples of whole blood also were obtained before and at 6, 12 and 24 h after the onset of treatment for determination of total and differential leukocyte numbers and lymphocyte blastogenic responses to mitogens. Both ACTH and cortisol were elevated in response to RIS; the profiles of these hormones over the 24-h bleeding period differed for RIS and CON lambs (P less than .001). (ABSTRACT TRUNCATED AT 250 WORDS)
High placental index and poor pregnancy outcomes: a retrospective study of 18 386 pregnancies

Abstract Introduction: Our aim was to state the correlation between placental index and pregnancy outcomes or in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) pregnancies. Materials and methods: We included in this retrospective study all singleton births in a third level clinic during the period 2001–2011 (n = 18 386). We divided placental index into quartiles and analyzed the differences between the groups in term of pregnancy outcomes. Then, we estimated crude and adjusted odds ratios (ORs) for placental index over the third centile of the distribution to correlate with pregnancy outcomes. We also analyzed the correlation between IVF/ICSI conceived pregnancies and placental index. Results: Poor pregnancy outcomes were overrepresented in the highest quartile of placental index distribution. Thus, placental index was higher in pregnancies characterized by pregnancy-related hypertensive disorders (PRHDs), small for gestational age infants, newborn needing cardiopulmonary resuscitation or hospitalization in neonatal intensive care unit. These findings were independent of maternal age, length of gestation at delivery, IVF/ICSI conception and ethnicity. For IVF/ICSI pregnancies, the OR for being over the third quartile of placental index distribution was 2.01 (CI.95 1.40–2.90) after adjustment for maternal age, length of gestation, ethnicity, birth weight, parity, fetal sex, alteration of glucose metabolism in pregnancy and PRHDs. Conclusions: We found a high placental index among pregnancies characterized by poor outcomes and conceived by IVF/ICSI.
Essential Role of Synoviolin in Embryogenesis*

We recently reported the importance of Synoviolin in quality control of proteins through the endoplasmic reticulum (ER)-associated degradation (ERAD) system and its involvement in the pathogenesis of arthropathy through its anti-apoptotic effect. For further understanding of the role of Synoviolin in vivo, we generated in this study synoviolin-deficient (syno–/–) mice by genetargeted disruption. Strikingly, all fetuses lacking syno died in utero around embryonic day 13.5, although Hrd1p, a yeast orthologue of Synoviolin, is non-essential for survival. Histologically, hypocellularity and aberrant apoptosis were noted in the syno–/– fetal liver. Moreover, definitive erythropoiesis was affected in non-cell autonomous manner in syno–/– embryos, causing death in utero. Cultured embryonic fibroblasts derived from syno–/– mice were more susceptible to endoplasmic reticulum stress-induced apoptosis than those from syno+/+ mice, but the susceptibility was rescued by overexpression of synoviolin. Our findings emphasized the indispensable role of the Synoviolin in embryogenesis.
PROTECTION OF ISCHAEMIC‐REPERFUSED RAT HEART BY DIMETHYLAMILORIDE IS ASSOCIATED WITH INHIBITION OF MITOCHONDRIAL PERMEABILITY TRANSITION

1 The aim of the present study was to assess whether protection afforded by the Na+/H+ exchanger blocker dimethylamiloride (DMA) is associated with inhibition of mitochondrial permeability transition (MPT). The effects of DMA were compared with those of cyclosporine (Cs) A, an inhibitor of MPT. 2 Rat hearts were Langendorff perfused with Krebs’–bicarbonate medium containing 10 mmol/L glucose and were subjected to 25 min no‐flow global ischaemia and 30 min reperfusion in the presence or absence of 10 µmol/L DMA or 0.2 µmol/L CsA. Cell viability was measured using tetrazolium stain. The MPT was determined by loading hearts with 2‐deoxy‐[3H]‐glucose (2DG), which enters mitochondria only during MPT. Total heart 2DG content as an estimation of the extent of tissue damage was also measured. To assess whether DMA has any direct effect on glycolysis, a cell‐free heart extract containing all the glycolytic enzymes was used. 3 Dimethylamiloride improved functional recovery (rate–pressure product) from 24 ± 7 to 68 ± 11% (P < 0.01) at reperfusion end, attenuated the increase in left ventricular end‐diastolic pressure (from 29 ± 7 to 6 ± 3% 10 min after reperfusion onset; P < 0.01), improved cell viability (from 21.2 ± 6.6 to 69.6 ± 7.1% at reperfusion end; P < 0.05) and lessened lactate accumulation at the end of ischaemia (119 ± 15 vs 163 ± 14 µmol/g dry weight; P < 0.05). Dimethylamiloride limited MPT : 2DG mitochondrial entrapment, being 33.1 ± 14.2 and 96.3 ± 14.0 at reperfusion end in the treated and control hearts, respectively (P < 0.05), and concomitantly raised total 2DG content (51.3 ± 4.4 vs 86.8 ± 1.7 × 103 d.p.m./g wet weight in control and treated groups, respectively; P < 0.05). Cyclosporine A improved functional recovery and attenuated the amplitude of ventricular diastolic pressure in ischaemic–reperfused hearts. It also reduced mitochondrial entrapment (67.3 ± 7.7%; P < 0.05 vs control) and increased total cell 2DG content (162.3 ± 1.3 × 103 d.p.m./g wet weight; P < 0.01 vs control) at the end of reperfusion. Dimethylamiloride did not affect glucose consumption and lactate production in the cell‐free heart extract. 4 In conclusion, DMA protects against the noxious effects of ischaemia–reperfusion and inhibits MPT, coinciding with present and previous findings concerning the effects of CsA. Dimethylamiloride also diminished lactate accumulation, although it did not exhibit any direct effect on glycolysis. These data suggest that blockade of Na+/H+ exchange by DMA attenuates the extent of MPT in ischaemic–reperfused rat heart.
Autonomy at the end of life: life-prolonging treatment in nursing homes—relatives’ role in the decision-making process

Background: The increasing number of elderly people in nursing homes with failing competence to give consent represents a great challenge to healthcare staff’s protection of patient autonomy in the issues of life-prolonging treatment, hydration, nutrition and hospitalisation. The lack of national guidelines and internal routines can threaten the protection of patient autonomy. Objectives: To place focus on protecting patient autonomy in the decision-making process by studying how relatives experience their role as substitute decision-makers. Design: A qualitative descriptive design with analysis of the contents of transcribed in-depth interviews with relatives. Participants: Fifteen relatives of 20 patients in 10 nursing homes in Norway. Results and Interpretations: The main findings reveal deficient procedures for including relatives in decision-making processes. Relatives have poor knowledge about the end of life, and there is little discussion about their role as substitute decision-makers for patients who are not competent to give consent. Few relatives understand the concept of patient autonomy. In Norway the treating physician is responsible for patient treatment. When relatives are included in discussions on treatment, they perceive themselves as responsible for the decision, which is a burden for them afterwards. This qualitative study describes relatives’ experiences, thus providing important information on the improvement potential with the main objective of safeguarding patient autonomy and caring for relatives. Conclusion: The study reveals failing procedures and thus a great potential for improvement. Both ethical and legal aspects must be addressed when considering patient autonomy.
DNA looping

DNA-looping mechanisms are part of networks that regulate all aspects of DNA metabolism, including transcription, replication, and recombination. DNA looping is involved in regulation of transcriptional initiation in prokaryotic operons, including ara, gal, lac, and deo, and in phage systems. Similarly, in eukaryotic organisms, the effects of enhancers appear to be mediated at least in part by loop formation, and examples of DNA looping by hormone receptor proteins and developmental regulatory proteins have been found. In addition, instances of looped structures have been found in replication and in recombination in both prokaryotes and eukaryotes. DNA loop formation may have different functions in different cellular contexts; in some cases, the loop itself is requisite for regulation, while in others the increase in the effective local concentration of protein may account for the effects observed. The ability of DNA to form loops is affected by the distance between binding sites; by the DNA sequence, which determines deformability and bendability; and by the presence of other proteins that exert an influence on the conformation of a particular sequence. Alteration of the stability of DNA loops and/or protein-DNA binding by extra- or intracellular signals provides responsivity to changing metabolic or environmental conditions. The fundamental property of site-specific protein binding to DNA can be combined with protein-protein and protein-ligand interaction to generate a broad range of physiological states.
Mortality Impact of Bt Transgenic Maize Roots Expressing eCry3.1Ab, mCry3A, and eCry3.1Ab Plus mCry3A on Western Corn Rootworm Larvae in the Field

ABSTRACT Mortality of the western corn rootworm, Diabrotica virgifera virgifera LeConte, larvae due to feeding on maize, Zea mays L. , expressing Bacillus thuringiensis Berliner (Bt) was evaluated in five Missouri sites in 2007, 2008, and 2009. Specifically, eCry3.1Ab (5307), mCry3A (MIR604), and eCry3.1Ab plus mCry3A proteins relative to survivorship on maize with the same genetic background without these genes (isoline maize) was evaluated. An average of 890.8 ± 152.3 beetles emerged from isoline plots, whereas average beetle emergence from 5307, MIR604, and 5307 × MIR604 was 1.9 ± 0.6,19.3 ± 6.3, and 0.8 ± 0.3, respectively, when averaged across 22 replications in five environments. Overall, 66, 50, 61, and 51% of beetles recovered from 5307, MIR604, 5307 × MIR604, and isoline maize, respectively, were female, and there was no significant difference between the number of male and female beetles that emerged from any of these treatments. Mortality due to 5307, MIR604, and 5307 × MIR604 was 99.79, 97.83, and 99.91%, respectively. There was an 8.0-d delay in time to 50% beetle emergence from 5307 compared with isoline maize, which was significantly later than to the other three maize lines. The average delay to 50% emergence from MIR604 and 5307 × MIR604 averaged 4.1 and 4.6 d, respectively later than 50% emergence from isoline maize. Female beetles had a significant delay in time to 50% emergence compared with male beetles from all treatments with the exception of 5307 × MIR604. Data are discussed in terms of insect resistance management in relation to other control measures for western corn rootworm.
Belinostat in patients with refractory or relapsed peripheral T-cell lymphoma: a perspective review

Peripheral T-cell lymphoma (PTCL) is a disease with poor prognosis and limited treatment options. Recent advances in cancer biology suggest that PTCL may be characterized by gross epigenetic dysregulation, which may help explain its sensitivity to histone deacetylase (HDAC) inhibitors. HDAC inhibitors have demonstrated significant activity in T-cell neoplasms and recently, the BELIEF trial evaluated belinostat leading to its approval in the US. This review discusses the development of belinostat, its mechanism of action, pivotal clinical trials, drug toxicity and its recent approval for patients with relapsed or refractory PTCL. Key clinical trials covered include phase I/II evaluation of belinostat in hematologic malignancies, cutaneous T-cell lymphoma (CTCL) and PTCL. In addition, the BELIEF trial in PTCL leading to FDA approval of belinostat is reviewed in detail.
Mediastinal lymphadenopathy and hazy mediastinal fat: new CT findings of congestive heart failure.

OBJECTIVE We describe two new CT findings of congestive heart failure (CHF): enlarged mediastinal lymph nodes and hazy heterogeneous mediastinal fat. MATERIALS AND METHODS Forty-six patients were retrospectively identified who had major and minor clinical signs of congestive heart failure and had undergone chest CT during their symptomatic period. Two radiologists reviewed the CT studies and by consensus documented the presence or absence of imaging findings of CHF, including interstitial abnormalities, vascular redistribution, axial thickening, pleural effusions, cardiac enlargement, and mediastinal abnormalities. RESULTS Smooth septal thickening, bilateral pleural effusions, vascular redistribution, and cardiac enlargement were the most common CT findings in patients with CHF. Enlarged mediastinal lymph nodes and hazy mediastinal fat were seen in 55% and 33% of cases, respectively. In a cohort of 17 patients with elevated pressures in the pulmonary capillary wedge documented within 24 hr of CT, CT scans revealed lymphadenopathy in 14 patients (82%) and inhomogeneous fat in 10 patients (59%). CONCLUSION Enlarged mediastinal lymph nodes and hazy mediastinal fat occur in patients with CHF and are revealed by CT. Lymphadenopathy in patients with CHF does not necessarily indicate malignancy or an infectious process.
Pharmacokinetics, Safety, and Tolerability of Caspofungin in Children and Adolescents

ABSTRACT Caspofungin is a parenteral antifungal that inhibits beta-1,3-d-glucan synthesis. Although licensed for adult use, the appropriate caspofungin dosing regimen in pediatric patients is not yet known. We therefore investigated the pharmacokinetics and safety of caspofungin in pediatric patients. Thirty-nine children (ages 2 to 11 years) and adolescents (ages 12 to 17 years) with neutropenia were administered caspofungin using either a weight-based regimen (1 mg/kg of body weight/day) or a body surface area regimen (50 mg/m2/day or 70 mg/m2/day). Plasma samples for caspofungin profiles were collected on days 1 and 4. These results were compared to those from adults treated with either 50 or 70 mg/day for mucosal candidiasis. In children receiving 1 mg/kg/day (maximum, 50 mg/day), the area under the concentration-time curve over 24 h (AUC0-24) was significantly smaller (46% after multiple doses) than that observed in adults receiving 50 mg/day (P < 0.001). In children and adolescents receiving 50 mg/m2/day (maximum, 70 mg/day), the AUC0-24 following multiple doses was similar to that for the exposure in adults receiving 50 mg/day. The AUC0-24 and concentration trough (at 24 h) in pediatric patients receiving the 50-mg/m2 daily regimen were consistent across the range of ages. Caspofungin was generally well tolerated in this study. None of the patients developed a serious drug-related adverse event or were discontinued for toxicity. These results demonstrate that caspofungin at 1 mg/kg/day in pediatric patients is suboptimal. Caspofungin administration at 50 mg/m2/day provides a comparable exposure to that of adult patients treated with 50 mg/day.