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Backgound. The existence of a “placental clock” which determines the duration of gestation has been previously proposed. It is related to placental CRH secretion and is active from an early phase in human pregnancy. Urocortin is a specific ligand for the corticotropin-releasing factor (CRF) receptor expressed by human trophoblast and fetal membranes. The purpose of this study was to evaluate whether urocortin concentrations in the early second trimester amniotic fluid might serve to predict preterm delivery. Method. The urocortin concentrations in early second trimester amniotic fluid were measured in 41 pregnancies with term delivery and in 41 pregnancies with preterm delivery by using an immunoradiometric assay. Conditional logistic regression analysis was used for statistical analysis. Results. Mean amniotic fluid urocortin concentrations in women with preterm labor were 1.55±0.63 ng/mL while those in women with term labor were 1.6±0.49 ng/mL (p: NS). No statistical significant results were found when comparing amniotic fluid urocortin concentrations in women with preterm premature rupture of membranes leading to preterm labor (𝑛=19) to women with term delivery without premature rupture of membranes. Conclusion. These results suggest that urocortin concentrations in the amniotic fluid of genetic amniocentesis are not predictive of preterm labor and birth.

Introduction and Aims: Neurological complications such as peripheral neuropathy are very common in the end-stage renal disease (ESRD) patients, occurring in 60-80% of this specific population. The aim of the present study was to examine whether a 9-month hybrid intradialytic exercise training program could alter motor and sensory nerve conduction study (NCS) parameters in hemodialysis population., Methods: Seventeen stable patients undergoing HD with no clinical evidence of uremic polyneuropathy were included in the study (15 M/2F, 59 ± 13.7 years). All patients completed a 9-month supervised exercise training program composed of both aerobic cycling and resistance training (hybrid) during HD. Functional capacity was assessed by a battery of tests, while pain levels and fatigue profile were assessed via validated questionnaires. Motor and sensory NCS on bilateral median, ulnar, peroneal and tibial nerves as well as F-wave were assessed using a full neurographic electromyography (EMG) assessment., Results: After the 9-month exercise training intervention, exercise capacity was increased by 65% and functional capacity by an average of 40%. The neurological assessment showed that conduction velocity from tibial and peroneal nerves was improved by 3.7% and 4.2%, respectively, while tibial F-wave latency and peroneal and sural nerve distal latency were significantly improved by 4.2%, 4.9% and 10%, respectively. Fatigue and pain were improved after the exercise intervention while fatigue score was positively correlated with conduction velocity and amplitude values., Conclusions: The results of the current study demonstrate that 9-month hybrid exercise training induces beneficial effects on both sensory and motor NCS parameters, improving conduction velocity and F-wave latency. Improvements in neural activity were accompanied by changes in fatigue score and pain-related aspects. The parallel improvement in motor nerve conduction velocity and its correlations with functional tests supports the hypothesis that exercise could be beneficial for preventing a decline in neural function in HD patients., (© 2022. The Author(s), under exclusive licence to Springer Nature B.V.)

Pesticides are widely-used chemicals commonly applied in agriculture for the protection of crops from pests. Depending on the class of pesticides, the specific substances may have a specific set of adverse effects on humans, especially in cases of acute poisoning. In past years, evidence regarding sequelae of chronic, low-level exposure has been accumulating. Cognitive impairment and dementia heavily affect a person's quality of life and scientific data has been hinting towards an association between them and antecedent chronic pesticide exposure. Here, we reviewed animal and human studies exploring the association between pesticide exposure, cognition and dementia. Additionally, we present potential mechanisms through which pesticides may act neurotoxically and lead to neurodegeneration. Study designs rarely presented homogeneity and the estimation of the exposure to pesticides has been most frequently performed without measuring the synergic effects and the possible interactions between the toxicants within mixtures, and also overlooking low exposures to environmental toxicants. It is possible that a Real-Life Risk Simulation approach would represent a robust alternative for future studies, so that the safe exposure limits and the net risk that pesticides confer to impaired cognitive function can be examined. Previous studies that evaluated the effect of low dose chronic exposure to mixtures of pesticides and other chemicals intending to simulate real life exposure scenarios showed that hormetic neurobehavioral effects can appear after mixture exposure at doses considered safe for individual compounds and these effects can be exacerbated by a coexistence with specific conditions such as vitamin deficiency. However, there is an overall indication, derived from both epidemiologic and laboratory evidence, supporting an association between exposure to neurotoxic pesticides and cognitive dysfunction, dementia and Alzheimer's disease., Competing Interests: Declaration of Competing Interest The authors declare that they have no conflict of interest., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background: Results from studies to date, regarding the role of chronic pesticide exposure on cognitive function remain contradictory., Objective: To investigate the relationship between self-reported pesticide exposure and cognitive function., Methods: Data from a population-based cohort study of older adults (HEllenic Longitudinal Investigation of Aging and Diet) in Greece was used. Pesticide exposure classification was based on 1) living in areas that were being sprayed; 2) application of spray insecticides/pesticides in their gardens; and 3) occupational application of sprays. Associations between z-scores of cognitive performance and self-reported pesticide exposure were examined with linear regression analyses. Adjusted models were applied, for all analyses., Results: Non-demented individuals who reported that they had been living in areas near sprayed fields, had poorer neuropsychological performance, compared to those who had never lived in such areas. Sub-analyses revealed poorer performance in language, executive and visual-spatial functioning, and attention. These associations remained after a sensitivity analysis excluding subjects with mild cognitive impairment., Conclusion: Self-reported exposure to pesticides was negatively associated with cognitive performance., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Objectives : Cardiac autonomic nervous system (ANS) dysfunction is a common feature in patients receiving hemodialysis (HD) therapy, whilst is associated with an increased risk of ventricular arrhythmias and sudden cardiac death. The aim of this study is to investigate and compare the hemodynamic changes and responses of ANS function in HD patients using pupillometry and Heart Rate Variability (HRV) parameters. Methods : Sixteen chronic kidney diseases (CKD) patients receiving HD (52.18 ± 17.7 years) underwent both pupillometric measurements using a portable handheld pupil-measuring device and standard HRV analysis pre HD, every hour and 30 min post-HD session under two different scenarios: at rest while the patient resting at HD bed and when the patient performed a single bout of intradialytic aerobic exercise lasting for 45 min during the second hour of the HD therapy. Results : No significant changes in ANS values were observed in neither of the pupillometric and the HRV values pre HD, for each hour and post-HD session. HRV parameters were significantly correlated with pupillometric parameters at pre HD and immediately after the single bout of intradialytic exercise. ANS activity did not differ during the conventional HD session and during the session included intradialytic exercise. Moreover, sympatho-vagal balance indices deriving from pupillometric assessment showed beneficial changes after the exercise event. Conclusion : Pupillometry is a promising and robust technique with fewer artifacts compared to HRV especially in studies involving exercise sessions. Thus, pupillometry can be used as a complementary tool in the evaluation of cardiac autonomic dysfunction.

Background: Precise temperature control in several key areas during cryopreservation of dormant, winter apple buds is critical for maximal survival., Objective: To consider the effects of pre-harvest temperature, the duration of incubation at -30°C and variation in rewarming rate on survival., Materials and Methods: Dormant winter buds of Malus x domestica cultivars were harvested with two different acclimation histories and cryopreserved with variation in incubation time at -30°C. Recovery from LN using slow, intermediate and rapid rewarming was investigated as well as preservation after prolonged storage at -4°C., Results: The effects on survival of preharvest temperature regime and an altered -30°C incubation regime are cultivar dependent and an increase in rewarming rate has a strong negative effect on recovery., Conclusion: Post-thaw survival of the winter-dormant buds can be compromised by increased temperature over a period as short as 5 days prior to bud harvest. Varying incubation times at -30°C produce variable, cultivar dependent, survival and moderate increases in rewarming rates can also radically reduce survival.

Objective: The objective of this study was to assess the pharmacokinetic and pharmacodynamic behavior of ticagrelor administered either as crushed (in the semi-upright sitting position) or as integral (in the supine position) tablets in ST-segment elevation myocardial infarction (STEMI) patients undergoing primary percutaneous coronary intervention (PCI)., Methods: We randomized 20 patients to ticagrelor 180 mg either as 2 integral tablets administered in the supine position (standard administration) or as 2 tablets crushed and dispersed, administered in the semi-upright sitting position. Blood samples were drawn for pharmacokinetic and pharmacodynamic assessment at randomization (0 h) and at 0.5, 1, 2, and 4 h., Results: At 1 h, ticagrelor plasma exposure and area under the plasma concentration-time curve from time zero to 1 h (AUC1) (co-primary endpoints) were higher in the crushed versus integral tablets group (median 586 vs. 70.1 ng/mL and 234 vs. 24.4 ng·h/mL, respectively), with a ratio of adjusted geometric means (95% confidence interval [CI]) of 12.67 (2.34-68.51) [p = 0.005] and 19.28 (3.51-106.06) [p = 0.002], respectively. Time to maximum plasma concentration was shorter in the crushed versus integral tablets group (median 2 vs. 4 h), with a ratio of adjusted geometric means (95% CI) of 0.69 (0.49-0.97) [p = 0.035]. Parallel findings were observed with AR-C124910XX (active metabolite). Platelet reactivity (VerifyNow(®)) at 1 h was lower with crushed versus standard administration with least squares estimates mean difference (95% CI) of 92 (-158.4 to 26.6) P2Y12 reaction units (p = 0.009)., Conclusions: In patients with STEMI undergoing primary PCI, ticagrelor crushed tablets administered in the semi-upright sitting position seems to lead to a faster-compared with standard administration-absorption, with stronger antiplatelet activity within the first hour., Trial Registration: ClinicalTrials.gov identifier: NCT02046486.

Ticagrelor loading dose (LD) increases adenosine plasma levels, which might interfere with fractional flow reserve (FFR) assessment because the latter is based on adenosine-induced hyperemia. In a prospective study, consecutive patients who underwent coronary angiography with at least 1 de novo stenosis >50% and <90% in severity amenable to intervention underwent FFR assessment using intravenous adenosine 140 μg/kg/min for 3 minutes. Patients were subsequently randomized to either ticagrelor 180 mg (n = 38) or control thienopyridine (n = 38) (prasugrel 60 mg [n = 28] or clopidogrel 600 mg [n = 10]), followed by a second FFR assessment of the target lesion 2 hours after drug. Pre-drug, steady hyperemia FFR (sFFR, median, first to third quartiles) was 0.82 (0.75 to 0.88) and 0.81 (0.75 to 0.88), p = 0.9, whereas post-drug, 0.82 (0.72 to 0.87) and 0.79 (0.73 to 0.86), p = 0.5, in thienopyridine and ticagrelor-treated patients, respectively. The primary end point of percent relative change in sFFR between pre- and post-drug periods was greater in ticagrelor- than thienopyridine-treated patients, -1.24 (-5.54 to 0.0) versus -0.51 (-3.68 to 3.21), p = 0.03, respectively. Absolute change in sFFR between pre- and post-drug periods was marginally higher in ticagrelor- than thienopyridine-treated patients -0.01 (-0.04 to 0.0) versus -0.005 (-0.03 to 0.02), p = 0.048, respectively. Reclassification of treatment decision at the sFFR ≤ 0.80 cutoff post-drug occurred in 6 (15.8%) versus 5 (13.2%) of ticagrelor- and thienopyridine-treated patients, respectively. In conclusion, after ticagrelor LD, an absolute and relative reduction in sFFR compared with thienopyridine LD is observed. Administration of ticagrelor should be considered as a potential source, albeit minor, of FFR variability., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Although HF has multiple causes amongst which coronary artery disease, hypertension and non-ischemic dilated cardiomyopathy are the most common, it results in the same final common pathway of neurohormonal activation and multiorgan dysfunction in the context of a salt-avid state. Contemporary pharmacologic HF therapy targets neurohormonal activation at multiple levels with β- blockers, angiotensin converting enzyme inhibitors, and aldosterone inhibitors, aiming in reversing both its systemic consequences, and the adverse heart remodeling, however is frequently hampered by side effects of the drugs, limiting its benefit. During the last 40 years studies of the gross and molecular aspects of the pathophysiology of HF convincingly converge to the conclusion that deranged calcium (Ca(2+)) handling in the cardiomyocytes plays a cardinal role in HF initiation and progression. The delicate and precise regulation of Ca(2+) cycling i.e. movement into and out of the cell, as well as into and out of the sarcoplasmic reticulum (SR), is finely tuned by numerous macromolecular proteins and regulatory processes like phosphorylation and dephosphorylation, and is severely deranged in HF. The common denominator in this scenario is Ca(2+) depletion of the SR, however loading of cardiomyocytes with Ca(2+) as a result of classic inotropic therapy has proved to be detrimental in the long term. Therefore, the mediator and/or regulatory components of the Ca(2+) cycling apparatus have been the focus of extensive research involving targeted pharmacologic and gene interventions aiming to a restoration of Ca(2+) cycling processes, thus improving inotropy and lucitropy in a more "physiologic" way in the failing myocardium.

Background: Ticagrelor may exert pleiotropic actions, beyond platelet inhibition, which are possibly adenosine-mediated. It has been suggested that in patients with coronary artery disease (CAD) ticagrelor may influence endothelial function., Objective: We aimed to assess the possibility of endothelial function deterioration following ticagrelor treatment cessation., Methods: This was a prospective, observational study, in stable CAD patients with prior percutaneous coronary intervention (PCI) for acute coronary syndrome manifested 1 year earlier, under ticagrelor maintenance dose (90 mg bid) and due to discontinue ticagrelor. Endothelial function was assessed by Peripheral Arterial Tonometry (EndoPat 2000 system, Itamar Medical, Caesarea, Israel) immediately after receiving the last tablet of ticagrelor (Day 0) and at Day 2 and Day 5 post-ticagrelor cessation. Reactive hyperaemia index (RHI) was calculated by automated software and endothelial dysfunction (ED) was defined as a RHI <1.67., Results: We identified 30 eligible patients with endothelial function assessment pre- and post-ticagrelor cessation (86.7% men, 13.3% with diabetes and 33.3% current smokers; mean age: 63.6±11.5 years). The study's primary endpoint of RHI at Day 5 did not differ significantly compared with RHI at Day 0, 1.69 (1.45-2.23) vs 1.81 (1.59-2.13). ED rate did not differ significantly between Day 5 and Day 0, 40 vs 33.3%, p=0.8, respectively. No differences in RHI or ED rate were observed between Day 2 and Day 0, 1.64 (1.54-2.04) vs 1.8 1(1.59-2.13), p=0.3 and 53.3 vs 33.3%, p=0.2, respectively. In stable CAD patients there is no evidence of deterioration in endothelial function after discontinuing ticagrelor.

Background: The influence of diabetes mellitus (DM) on platelet reactivity (PR) in prasugrel or ticagrelor treated patients is not well studied., Methods: In an observational study involving 777 patients with acute coronary syndrome undergoing percutaneous coronary intervention treated by either prasugrel 10 mg od (n = 315) or ticagrelor 90 mg bid (n = 462), platelet function was assessed using the VerifyNow P2Y12 function assay (in PRU) at one month post intrvention., Results: In the overall population, ticagrelor and insulin-treated DM affected PR, with a decrease in log by 0.88 (corresponding to a 58 % decrease in PR) compared to prasugrel-treated patients (p < 0.001), and an increase in log by 0.26 (corresponding to a 30 % increase in PR) compared to non-diabetic patients (p = 0.01), respectively. PR in prasugrel-treated patients differed significantly by DM status: 70.0 (36.3-113.0) in non-diabetic vs 69.0 (44.5-115.3) in non insulin-treated diabetic vs 122.0 (69.0-161.0) in insulin-treated diabetic patients, p for trend = 0.01. No differences were observed in ticagrelor-treated patients. By multivariate analysis, in prasugrel-treated patients insulin-treated DM was the only factor predicting PR, with log of PR increased by 0.42 (corresponding to a 52 % increase in PR) compared to non-diabetic patients (p = 0.001). No factor was found to affect PR in ticagrelor-treated patients., Conclusions: Patients with insulin-treated DM treated with prasugrel post PCI have higher PR, than patients without DM or non insulin-treated diabetic patients treated with this drug. Ticagrelor treated patients have overall lower PR than patients on prasugrel, independent of DM status or insulin treatment., Trial Registration: Clinical Trials Gov. NCT01774955.

Platelet reactivity (PR) and bleeding events following therapy with ticagrelor vs prasugrel have not been adequately studied. We aimed to compare PR and bleeding events in patients with acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (PCI) while on ticagrelor vs prasugrel for one month. Consecutive patients who were discharged either on ticagrelor 90 mg bid maintenance dose (MD) or prasugrel 10 mg MD were invited for PR assessment (VerifyNow, in PRU) at one month. High PR (HPR) was defined as >208 PRU. Bleeding events [Bleeding Academic Research Consortium (BARC) classification] were monitored. Out of 937 screened patients, 512 were analysed, 278 under ticagrelor MD and 234 under prasugrel MD. PR at 30 days (C-statistic of the propensity score model 0.63, 0.58-0.67 95% CI, p<0.001) was lower when on ticagrelor compared with prasugrel (33.3, 95% CI 29.3-37.3 vs 84.6, 95% CI 73.6-95.6, p<0.001). In the analysed population more BARC type 1 bleeding events were observed with ticagrelor compared to prasugrel (36.7% vs 28.2%, p=0.047). In 221 propensity score matched pairs, BARC type 1 bleeding rate was marginally higher in ticagrelor vs prasugrel treated patients (35.7% vs 27.1%, p=0.05). BARC type ≥2 events did not differ between groups 5 (2.3%) vs 5 (2.3%). HPR rate was higher for prasugrel-treated patients (5.4% vs 0%, p<0.001). In conclusion, in patients with ACS undergoing PCI, ticagrelor MD produces a significantly higher platelet inhibition compared to prasugrel MD. This pharmacodynamic difference might be associated with more nuisance bleeding events with ticagrelor use.

In a continuing study to improve the efficiency of dormant bud cryopreservation for tissues hardened in maritime climates, the water status of dormant buds was monitored between -4 degree C and recovery from liquid nitrogen (LN). Measurement of water content, simple thermal analysis and differential scanning calorimetry were employed. Buds did not lose water during cooling to, or holding at -30 degree C indicating that cryodehydration and/or other adaptive responses contributed during this essential step. A bud exotherm that was an artefact of warming was detected due to necessary handling at -4 degree C before cooling to -30 degree C. There were no significant differences between cultivars with respect to water status at -30 degree C or immediately upon rewarming from LN despite significant differences in post-LN survival. Buds rehydrated in 5 days, but up to 14 days may be needed for recovery for some cultivars. In some instances buds could be grafted without rehydration, taking up water across the early graft union.

Cognitive impairment (CI) is increasingly recognized as a common adverse consequence of heart failure (HF). Although the exact mechanisms remain unclear, microembolism, chronic or intermittent cerebral hypoperfusion, and/or impaired cerebral vessel reactivity that lead to cerebral hypoxia and ischemic brain damage seem to underlie the development of CI in HF. Cognitive decline in HF is characterized by deficits in one or more cognition domains, including attention, memory, executive function, and psychomotor speed. These deficits may affect patients' decision-making capacity and interfere with their ability to comply with treatment requirements, recognize and self-manage disease worsening symptoms. CI may have fluctuations in severity over time, improve with effective HF treatment or progress to dementia. CI is independently associated with disability, mortality, and decreased quality of life of HF patients. It is essential therefore for health professionals in their routine evaluations of HF patients to become familiar with assessment of cognitive performance using standardized screening instruments. Future studies should focus on elucidating the mechanisms that underlie CI in HF and establishing preventive strategies and treatment approaches.

The established protocol for the cryopreservation of winter-dormant Malus buds requires that stem explants, containing a single, dormant bud are desiccated at -4 degree C, for up to 14 days, to reduce their water content to 25-30 percent of fresh weight. Using three apple cultivars, with known differences in response to cryopreservation, the pattern of evaporative water loss has been characterised, including early freezing events in the bud and cortical tissues that allow further desiccation by water migration to extracellular ice. There were no significant differences between cultivars in this respect or in the proportions of tissue water lost during the desiccation process. Differential Scanning Calorimetry (to -90 degree C) of intact buds indicated that bud tissues of the cultivar with the poorest response to cryopreservation had the highest residual water content at the end of the desiccation process and froze at the highest temperature.

The widely-adopted protocol for the cryopreservation of winter buds of fruit trees, such as Malus and Pyrus, was developed in a region with a continental climate, that provides relatively hard winters with a consequent effect on adaptive plant hardiness. In this study the protocol was evaluated in a typical maritime climate (eastern Denmark) where milder winters can be expected. The survival over two winters was evaluated, looking at variation between seasons and cultivars together with the progressive reduction in survival due to individual steps in the protocol. The study confirms that under such conditions significant variation in survival can be expected and that an extended period of imposed dehydration at -4 degree C is critical for bud survival. The occurrence of freezing events during this treatment suggests that cryodehydration may be involved, as well as evaporative water loss. To optimize the protocol for maritime environments, further investigation into the water status of the explants during cryopreservation is proposed.

Objectives: Studies investigating the association between angiotensin-converting enzyme (ACE) insertion/deletion (I/D) polymorphism and the risk of intracerebral hemorrhage (ICH) have provided conflicting results. Moreover, it is possible that the ACE I/D polymorphism may not represent the functional variant of the gene. The objective of this study was to clarify the influence of the ACE gene region on the risk of ICH by genotyping tag polymorphisms along ACE gene in two independent ethnically different cohorts., Methods: We included 250 Greek and 169 Polish unrelated patients with ICH and 250 Greek and 322 Polish normal controls in the study. To cover the majority of the genetic variability across the extended ACE gene region, we identified five tag single nucleotide polymorphisms (rs4343, rs4461142, rs7221780, rs8066276, rs8066114) from the HapMap using a pairwise tagging approach and an r2 greater than or equal to 0.8. Single nucleotide polymorphisms and haplotypes were analyzed for associations with ICH risk, ICH subtype (lobar/nonlobar), and age of disease onset using logistic and Cox regression models. Correction for multiple comparisons was carried out., Results: In the Polish cohort, we observed a trend toward an association between the rs4461142 and the age of ICH onset (hazard ratio 0.50, 95% confidence interval 0.27-0.90, P=0.02). A common haplotype (GTCTC) also showed a trend for increased ICH risk in the Polish cohort (odds ratio 0.19, 95% confidence interval 0.04-0.85, P=0.02). These results were not replicated in the Greek cohort., Conclusions: Our results did not provide clear evidence for a role of ACE gene in the development of ICH.

Background: Vaginitis is a common cause of complaints in women in various parts of the world. Through our literature search, we identified noteworthy differences in the etiology of vaginitis based on the geographic location. This study was conducted to describe microbial etiology in a population of symptomatic women with vaginitis in Greece., Material/methods: Data for pathogens isolated from cultures of vaginal fluid specimens or identified with microscopy testing of such specimens of women with symptomatic vaginitis who were examined at "Lito" Private Obstetric/Gynecological Hospital, Athens, Greece, during the period 1/2003-12/2006 were analyzed retrospectively., Results: During this period, 1632 women were examined. The mean age of the patients was 28 years, ranging from 18 to 57 years. Three hundred and eighty five from 1632 cultures/tests contributed no pathogen, whereas 1247/1632 cultures/tests were positive. Of the isolates, in which twelve species were identified, 504 (40.4%) were Gardnerella vaginalis, 530 (42.5%) Candida spp, and 101 (8.1%) Trichomonas vaginalis. Less usual isolates were Escherichia coli, Streptococcus agalactiae, Enterococcus spp., Streptococcus viridans, Staphylococcus epidermidis, Peptostreptococcus spp., and Staphylococcus saprophyticus., Conclusions: The authors believe that this study adds to the relevant literature of information regarding the pathogens implicated in patients with symptomatic vaginitis by reporting data from a cohort of patients in Greece. Ninety-one percent of the isolated and identified pathogens from vaginal cultures of symptomatic Greek women included Candida albicans, Gardnerella vaginalis, and Trichomonas vaginalis, with the first two species representing the great majority.