Miracle-dz/UniFAR-FTUs huggingface dataset:
Transplantation of young ovaries restored cardioprotective influence in postreproductive‐aged mice

The female cardioprotective advantage, present in mammals of a reproductively competent age, is lost during the transition to a postreproductive state. The role of reproductive hormones in this transition is most evident in women with premature ovarian failure, where reduced estrogen production has been associated with an increased incidence of early death from cardiovascular disease. Previously, we reported that postreproductive‐aged mice that received young ovaries displayed an increased life span. Subsequent histopathological analysis suggested the presence of a cardioprotective effect associated with the restoration of ovarian influence. This restoration in postreproductive‐aged mice produced a sharp decrease in evidence of significant cardiomyopathy at death, compared with sham‐transplanted mice (36.0% vs. 73.3%, respectively). Within the intact transplant group, evidence of cardiomyopathy at death was decreased in mice that were reproductively cycling at the time of transplant, compared with acyclic mice (26.7% vs. 50.0%, respectively). This observation reflects the importance of timing in restoration of ovarian influence in this study. Transplantation of young ovaries to intact, postreproductive‐aged female mice provided significant, long‐term restoration of a cardioprotective benefit, similar to that previously present during a reproductively competent age. In these mice, restoration of ovarian influence through ovarian transplantation may, in effect, have postponed the advance of age‐associated cardiomyopathy to a point where the disease did not reach a clinically relevant threshold during the lifetime of the recipients. These results offer support for previous clinical observations suggesting that hormone replacement therapy can produce divergent results if initiated during the perimenopausal period, compared with the postmenopausal ages.
Age‐related decline in osteoblastogenesis and 1α‐hydroxylase/CYP27B1 in human mesenchymal stem cells: stimulation by parathyroid hormone

With aging, there is a decline in bone mass and in osteoblast differentiation of human mesenchymal stem cells (hMSCs) in vitro. Osteoblastogenesis can be stimulated with 1,25‐dihydroxyvitamin D3 [1,25(OH)2D3] and, in some hMSCs, by the precursor 25‐hydroxyvitamin D3 (25OHD3). CYP27B1/1α‐hydroxylase activates 25OHD3 and, to a variable degree, hMSCs express CYP27B1. In this study, we tested the hypotheses (i) that age affects responsiveness to 25OHD3 and expression/activity of CYP27B1 in hMSCs and (ii) that parathyroid hormone (PTH) upregulates CYP27B1 in hMSCs, as it does in renal cells. There were age‐related declines in osteoblastogenesis (n = 8, P = 0.0286) and in CYP27B1 gene expression (n = 27, r = −0.498; P = 0.008) in hMSCs. Unlike hMSCs from young subjects (≤50 years), hMSCs from older subjects (≥55 years) were resistant to 25OHD3 stimulation of osteoblastogenesis. PTH1‐34 (100 nm) provided hMSCs with responsiveness to 25OHD3 (P = 0.0313, Wilcoxon matched pairs test) and with two episodes of increased 1,25(OH)2D3 synthesis, of cAMP response element binding protein (CREB) activation, and of CYP27B1 upregulation. Both increases in CYP27B1 expression by PTH were obliterated by CREB‐siRNA or KG‐501 (which specifically inhibits the downstream binding of activated CREB). Only the second period of CREB signaling was diminished by AG1024, an inhibitor of insulin‐like growth factor‐I receptor kinase. Thus, PTH stimulated hMSCs from elders with responsiveness to 25OHD3 by upregulating expression/activity of CYP27B1 and did so through CREB and IGF‐I pathways.
Persistent degenerative changes in thymic organ function revealed by an inducible model of organ regrowth

The thymus is the most rapidly aging tissue in the body, with progressive atrophy beginning as early as birth and not later than adolescence. Latent regenerative potential exists in the atrophic thymus, because certain stimuli can induce quantitative regrowth, but qualitative function of T lymphocytes produced by the regenerated organ has not been fully assessed. Using a genome‐wide computational approach, we show that accelerated thymic aging is primarily a function of stromal cells, and that while overall cellularity of the thymus can be restored, many other aspects of thymic function cannot. Medullary islet complexity and tissue‐restricted antigen expression decrease with age, representing potential mechanisms for age‐related increases in autoimmune disease, but neither of these is restored by induced regrowth, suggesting that new T cells produced by the regrown thymus will probably include more autoreactive cells. Global analysis of stromal gene expression profiles implicates widespread changes in Wnt signaling as the most significant hallmark of degeneration, changes that once again persist even at peak regrowth. Consistent with the permanent nature of age‐related molecular changes in stromal cells, induced thymic regrowth is not durable, with the regrown organ returning to an atrophic state within 2 weeks of reaching peak size. Our findings indicate that while quantitative regrowth of the thymus is achievable, the changes associated with aging persist, including potential negative implications for autoimmunity.
Linkage of cardiac gene expression profiles and ETS2 with lifespan variability in rats

Longevity variability is a common feature of aging in mammals, but the mechanisms responsible for this remain largely unknown. Using microarray datasets coupled with prediction analysis of microarrays (PAM), we identified a set of 252 cardiac transcripts predictive of relative lifespan in Wistar and Fisher 344 rats. Prediction analysis of microarrays ‘tests’ of rat heart transcriptomes from a third longer lived Fisher × Norway Brown rat strain validated the predictive value of this gene subset. The expression patterns of these genes were highly conserved, and corresponding promoter regions were employed to identify common cis–elements and trans‐activating factors implicated in their control. Specifically, four transcription factors (Max, Ets2, Erg, and Msx2) present in heart displayed longevity‐dependent, strain‐independent changes in abundance, but only ETS2 had an expression profile that directly correlated with the relative lifespan gene set. In heart, ETS2 was prevalent in cardiomyocytes (CMs) and showed a high degree of myocyte‐to‐myocyte variability predominantly in adult rat hearts prior to the exponential increase in the rate of mortality. Exclusively in this group, elevated ETS2 significantly overlapped with TUNEL staining in heart myocytes. In response to sympathetic stimuli, ETS2 is also up‐regulated, and functionally, adenovirus‐mediated over‐expression of ETS2 promotes apoptosis‐inducing factor‐mediated, caspase‐independent programmed necrosis exclusively in CMs that can be fully inhibited by the PARP‐1 inhibitor DPQ. We conclude that variations in ETS2 abundance in hearts of adult rodents and the associated loss of CMs contribute at least partially, to the longevity variability observed during normal aging of rats through activation of programmed necrosis.
High tryptophan diet reduces CA1 intraneuronal β‐amyloid in the triple transgenic mouse model of Alzheimer’s disease

Alzheimer’s disease (AD) is a progressive neurodegenerative disease that impairs mnesic functions. The histopathology of the disease is manifested by the accumulation of intracellular β‐amyloid (Aβ) and subsequent formation of neuritic plaques as well as the presence neurofibrillary tangles in specific brain regions associated with learning and memory including the hippocampus. Here, we analysed the effect of chronic (1 month) food diets containing low (LTrP), normal (NTrP) and high tryptophan (HTrP), 0.04, 0.20 and 0.40 g/100 g, respectively, on CA1 serotonin transporter (SERT) fibre density, intraneuronal Aβ deposition and total number of serotonergic (5‐HT) neurons in an AD triple transgenic (3xTg‐AD) mouse model. Nontransgenic (non‐Tg) animals fed with HTrP displayed increased SERT fibre density in CA1 (35%) and in stratum lacunosum moleculare (S.Mol) (48%) compared to LTrP diet. Transgenic animals showed increased SERT fibre density in CA1 S.Mol compared to diet‐matched non‐Tg irrespective of dietary tryptophan content (104% for LTrP, 74% for NTrP and 35% for HTrP); no differences were observed in the total number of 5‐HT neurons neither in the dorsal nor in the median raphe nuclei. However, and more relevant to AD, HTrP diet reduced intraneuronal Aβ density (by a 17%) in transgenic animals compared to transgenic animals fed with NTrP diet. Our results show that increased dietary TrP intake reduces intraneuronal Aβ load in the 3xTg‐AD mouse model of AD, suggesting that enhanced TrP intake and in consequence a potential increase in 5‐HT neurotransmission may be effective in reducing plaque pathology in AD.
Chromosome cohesion decreases in human eggs with advanced maternal age

Aneuploidy in human eggs increases with maternal age and can result in infertility, miscarriages, and birth defects. The molecular mechanisms leading to aneuploidy, however, are largely unknown especially in the human where eggs are exceedingly rare and precious. We obtained human eggs from subjects ranging from 16.4 to 49.7 years old following in vitro maturation of oocyte‐cumulus complexes isolated directly from surgically removed ovarian tissue. A subset of these eggs was used to investigate how age‐associated aneuploidy occurs in the human. The inter‐kinetochore distance between sister chromatids increased significantly with maternal age, indicating weakened cohesion. Moreover, we observed unpaired sister chromatids from females of advanced age. We conclude that loss of cohesion with increasing maternal age likely contributes to the well‐documented increased incidence of aneuploidy.
Nutrition and nutritional supplementation

Skin acts as a natural barrier between internal and external environments thus plays an important role in vital biological functions such as protection against mechanical/chemical damages, micro-organisms, ultraviolet damage. Nutrition has a critical impact on strengthening skins' capabilities to fight against these multiple aggressions. Nutritional deficiencies are often associated with skin health disorders, while diets can either positively or negatively influence skin condition. More recently, the concept of nutritional supplementation has emerged as a new strategy in the daily practice of dermatology as well as a complementary approach to topical cosmetics in the field of beauty. Focusing on human clinical data, this paper proposes to illustrate the link between skin health and nutrition and to exemplify the beneficial actions of nutritional supplementation in skin health and beauty.
Association of findings in flow‐volume spirometry with high‐resolution computed tomography signs in asbestos‐exposed male workers

Introduction: Disorders of pulmonary tissue and pleura are visualized by findings in high‐resolution computed tomography (HRCT), and the impairment caused by these findings is assessed by pulmonary function tests. Our aim was to determine how some commonly used spirometric variables are related to certain HRCT signs, in order to find out which HRCT signs are associated with restrictive and which with obstructive ventilatory impairment.
Platelet counts in adults with iron deficiency anemia

In adults with iron deficiency anemia (IDA), abnormal platelet counts were seen in several studies. However we retrospectively examined the clinical records of a larger number of adults with IDA to assess abnormal platelet counts. From November 2006 to April 2008, 615 consecutive adults (73 men and 542 women; age range, 16–88 years) with IDA were included in this study. The mean initial hemoglobin was 9.0 ± 1.8 g/dL (range 2.7–12.8 g/dL), and the mean initial platelet count was 304 × 103/µL ± 92.3 (range, 105–700 × 103/µL). The initial platelet counts were normal in 520 (84.6%) adults with IDA. Thrombocytosis (>400 × 103/µL) and thrombocytopenia (<150 × 103/µL) were detected in 82 (13.3%) and 13 (2.1%) adults with IDA, respectively. In conclusion, thrombocytosis was seen at lower rates in our study. Furthermore, this study shows that mild thrombocytopenia is not so rare in adults with IDA.
Normovolemia defined according to cardiac stroke volume in healthy supine humans

Background: Both hypovolemia and a fluid overload are detrimental for outcome in surgical patients but the effort to establish normovolemia is hampered by the lack of an operational clinical definition. Manipulating the central blood volume on a tilt table demonstrates that the flat part of the Frank‐Starling curve is reached when subjects are supine and that finding may be applicable for a clinical definition of normovolemia. However, it is unknown whether stroke volume (SV) responds to an increase in preload induced by fluid administration.
pidemiology and prevalence of Toxoplasma gondii infection n the Iberian hare ( Lepus granatensis )

Hares are important game species in Europe and their meat is consumed by humans. Toxoplasmosis is an important cause of mortality in hares in Nordic countries but little is known of Toxoplasma gondii infection in the Iberian hare (Lepus granatensis). Sera from 298 Iberian hares from Navarra (North Spain) were assayed for antibodies against T. gondii by the modified agglutination test. The samples were collected at necropsy during three consecutive years (2009–2011). Titers of 1:25 and higher were found in 34 hares (11.4%; CI95%: 7.8–14.9). Significant differences in seroprevalence were observed among geographical areas, years of sampling and age groups. The highest seroprevalence and the highest titers were observed in 2009, indicating fluctuating rates of transmission. Significantly higher seroprevalence was observed in the juvenile age group compared to the adult hare group. More than 40% of juvenile hares were seropositive the first year of study, seroprevalence drastically decreased in the juvenile animals sampled in the second year and was negligible in those sampled in the third year in this group. No clinical cases were detected in the study area and T. gondii was not detected by PCR in the liver of the 34 seropositive hares tested. These data may indicate that most juvenile seropositive hares did not survive as adults in the consecutive year or that there is a short-term humoral immune response against T. gondii in Iberian hares.
Single particle analysis: Methods for detection of platelet extracellular vesicles in suspension (excluding flow cytometry)

Abstract Extracellular vesicles (EVs) are small, membrane-bound particles released by all cell types, including abundant release by platelets. EVs are a topic of increasing interest in the academic and clinical community due to their increasingly recognised and diverse role in normal biology as well as in disease. However, typical analysis methods to characterise EVs released by cultured cells or isolated from whole blood or other body fluids are restricted to bulk analysis of all EVs in a sample. In this review, we discuss the motivation for analysis of individual EVs, as well as discuss three emerging methods for physical and chemical characterisation of individual EVs: nanoparticle tracking analysis, tunable resistive pulse sensing and Raman spectroscopy. We give brief descriptions of the working principles of each technique, along with a review noting the benefits and limitations of each method as applied to detection of single EVs.
Diurnal and position‐induced variability of impedance cardiography measurements in healthy subjects

Cardiovascular (CV) parameters and their measurements are subject to variation. In this study, we evaluated the reproducibility of impedance cardiography (ICG) measurements following orthostatic and diurnal challenges for a set of 22 CV parameters in ten randomly selected healthy nonpregnant women. A standard protocol was used to record a consecutive series of measurements for each parameter before and after three position changes. This series of measurements was performed twice (AM and PM sessions). For each parameter, measurement‐shift following position change was evaluated at 5% cutoff and compared between sessions. Intra‐ and intersession intraclass correlation (ICC) was calculated for individual measurements per position using repeated‐measures analysis of variance. Intra‐ and intersession Pearson’s correlation coefficient (PCC) was calculated for mean values per position. Intersession correlation for measurement‐shift following position change was 0·42 (5/12) for pressure parameters, whereas this was 0·96 (52/54) for other parameters. Inter‐ and intrasession ICC for individual measurements varied between 0·02 and 1 for all parameters, however inter‐ and intrasession PCC for mean values was consistently >0·80 for stroke volume (SV), stroke index (SI), cardiac output (CO), acceleration and velocity index (ACI and VI), thoracic fluid content (TFC), TFC index (TFCI) and heart period duration (HPD). We conclude that in healthy subjects under standardised conditions, reproducibility of means of multiple ICG measurements is high for SV, SI, CO, ACI, VI, TFC, TFCI and HPD. From our data, we cannot draw conclusions on trends in diseased subjects.
Sustained hyperaemia stimulus is necessary to induce flow‐mediated dilation of the human brachial artery

We studied the relative importance of the magnitude and duration of the shear stimulus to induce flow‐mediated dilation (FMD) in the brachial artery of 10 healthy men by ultrasound imaging. The shear stress stimulus was induced by different durations of reactive hyperaemia following 15‐min forearm occlusion. The control condition of continuous postocclusion hyperaemia was compared to 20, 40 and 60 s of reactive hyperaemia followed by reapplication of circulatory arrest for 2 min and a second cuff release. In response to the first cuff release, peak shear rate was not different between conditions; total shear during the first minute was reduced in the 40 s and further reduced in the 20 s conditions. FMD in control (10·0 ± 3·0%), 60 s (10·5 ± 3·2%) and 40 s (7·8 ± 3·6%) were greater than the 20‐s condition (2·9 ± 2·8%). At second cuff release, peak shear of the 20‐s condition was slightly reduced from the first release, but 40 and 60‐s conditions were progressively reduced. Total shear to peak dilation was reduced after the second cuff release for the 20 and 40‐s conditions and further after the 60‐s condition. FMD was maintained in the 20‐s condition (8·3 ± 3·7%) but reduced in the 40‐s (3·7 ± 1·7%) and 60‐s conditions (1·5 ± 2·6%). FMD was not related to peak shear rate after the first occlusion (r = 0·003) but was after the second cuff release (r = 0·32, P = 0·004). The FMD response was correlated with the total shear to time of peak diameter after the first (r = 0·35, P<0·001) and the second (r = 0·25, P = 0·009) cuff release.
Leadership styles of nurse managers and registered sickness absence among their nursing staff

Background: Sickness absence leads to understaffing and interferes with nursing efficiency and quality. It has been reported in literature that managerial leadership is associated with self-reported sickness absence in the working population. Purposes: This study investigated the relationship between managerial leadership and sickness absence in health care by associating nurse managers' leadership styles with registered sickness absence among their nursing staff. Methodology: The cross-sectional study included 699 nurses working in six wards (staff range = 91-140 employees) of a Dutch somatic hospital employing a total of 1,153 persons. The nurse managers heading the wards were asked to complete the Leadership Effectiveness and Adaptability Description questionnaire for situational leadership. The Leadership Effectiveness and Adaptability Description scores were linked to employer-registered nursing staff sickness absence. Findings: High relationship-high task behavior (odds ratio [OR] = 0.76, 95% confidence interval [CI] = 0.65-0.85) and high relationship-low task behavior (OR = 0.37, 95% CI = 0.14 -0.98) were inversely related to the number of short (one to seven consecutive days) episodes of sickness absence among the staff. Low relationship-high task styles (OR = 2.44, 95% CI = 1.14-5.22) as well as low relationship-low task styles (OR = 2.44, 95% CI = 1.26-4.71) were positively associated with the number of short episodes of sickness absence. However, the leadership styles only explained 10% of the variance in short episodes of sickness absence. Practice Implications: Leadership styles are associated with registered sickness absence. The nursing staff of relationship-oriented nurse managers has fewer short episodes of sickness absence than the staff of task-oriented managers. Training nurse managers in relational leadership styles may reduce understaffing and improve nursing efficiency and quality.
A 2D non‐invasive ultrasonic method for simultaneous measurement of arterial strain and flow pattern

Many cardiovascular diseases are closely associated with the mechanical properties of arterial wall and hemodynamic parameters. Simultaneous measurements of the arterial strain and flow pattern may aid diagnosis of cardiovascular diseases and may be useful to study fluid‐structure interaction between blood and vessel. This paper proposes a 2D non‐invasive ultrasonic method to simultaneously measure arterial strain and flow pattern with sub‐pixel accuracy.
Marked bleeding diathesis in patients with platelet dysfunction due to a novel mutation in RASGRP2, encoding CalDAG-GEFI (p.Gly305Asp)

ABSTRACT Congenital platelet function disorders are often the result of defects in critical signal transduction pathways required for platelet adhesion and clot formation. Mutations affecting RASGRP2, the gene encoding the Rap GTPase activator, CalDAG-GEFI, give rise to a novel, and rare, group of platelet signal transduction abnormalities. We here report platelet function studies for two brothers (P1 and P2) expressing a novel variant of RASGRP2, CalDAG-GEFI(p.Gly305Asp). P1 and P2 have a lifelong history of bleeding with severe epistaxis successfully treated with platelet transfusions or rFVIIa. Other bleedings include extended hemorrhage from minor wounds. Platelet counts and plasma coagulation were normal, as was αIIbβ3 and GPIb expression on the platelet surface. Aggregation of patients’ platelets was significantly impaired in response to select agonists including ADP, epinephrine, collagen, and calcium ionophore A23187. Integrin αIIbβ3 activation and granule release were also impaired. CalDAG-GEFI protein expression was markedly reduced but not absent. Homology modeling places the Gly305Asp substitution at the GEF-Rap1 interface, suggesting that the mutant protein has very limited catalytic activity. In summary, we here describe a novel mutation in RASGRP2 that affects both expression and function of CalDAG-GEFI and that causes impaired platelet adhesive function and significant bleeding in humans.
Effects of exercise prescription on daily physical activity and maximal exercise capacity in coronary artery disease patients with and without type 2 diabetes

Promotion of and adherence to increased physical activity (PA) is an important part of the prevention and treatment of coronary artery disease (CAD). We hypothesized that individually tailored home‐based exercise prescriptions will increase long‐term PA and maximal exercise capacity among CAD patients without and with type 2 diabetes (CAD+T2D).