The aim of this study was to evaluate phenolic composition, antioxidant potential, and lipolytic events in raw milk obtained from goat fed a dietary supplementation with olive leaves (OL), a ...by-product of the olive oil production chain. For this purpose, 30 Saanen goats were randomly allocated into 2 groups of 15 goats each: the control group received a standard diet that was prepared by taking into account the nutritional needs of lactating goats, whereas the experimental group (EG) was fed with an OL-supplemented diet (10% on a dry matter basis). At the end of the 30 d of the trial, the individual milk samples were collected and immediately analyzed for total phenolic content and antioxidant activity (AOA). Subsequently, the individual phenolic compounds have been identified and quantified through an ultra-high-performance liquid chromatography system and a characterization of free fatty acids released in milk has been performed. The results showed a positive effect of dietary OL supplementation in improving total phenolic content and AOA; furthermore, 19 phenolic compounds, including phenolic acids, flavonoids, simple phenols, and secoiridoids, have been identified in EG milk. In addition to this, a reduced accumulation of free fatty acids has been found in EG milk, and this finding leads us to hypothesize an inhibitory action of the identified phenolic compounds toward the enzymes responsible for lipolytic events. The use of the molecular docking approach verified the interactions, defining a fairly interesting framework for cinnamic acid, which should be able to noncovalently bind these enzymes, interfering with the recruitment of the substrate and therefore, slowing down their hydrolytic activity. In any case, this information will be subjected to in vitro evaluations for an accurate characterization of the biochemical mechanisms that can be established in milk naturally enriched with bioactive compounds.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
A Val(66)Met single-nucleotide polymorphism (SNP) in the brain-derived neurotrophic factor (BDNF) gene impairs activity-dependent BDNF release in cultured hippocampal neurons and predicts impaired ...memory and exaggerated basal hippocampal activity in healthy humans. Several clinical genetic association studies along with multi-modal evidence for hippocampal dysfunction in schizophrenia indirectly suggest a relationship between schizophrenia and genetically determined BDNF function in the hippocampus. To directly test this hypothesized relationship, we studied 47 medication-free patients with schizophrenia or schizoaffective disorder and 74 healthy comparison individuals with genotyping for the Val(66)Met SNP and (15)OH(2)O positron emission tomography (PET) to measure resting and working memory-related hippocampal regional cerebral blood flow (rCBF). In patients, harboring a Met allele was associated with significantly less hippocampal rCBF. This finding was opposite to the genotype effect seen in healthy participants, resulting in a significant diagnosis-by-genotype interaction. Exploratory analyses of interregional resting rCBF covariation revealed a specific and significant diagnosis-by-genotype interaction effect on hippocampal-prefrontal coupling. A diagnosis-by-genotype interaction was also found for working memory-related hippocampal rCBF change, which was uniquely attenuated in Met allele-carrying patients. Thus, both task-independent and task-dependent hippocampal neurophysiology accommodates a Met allelic background differently in patients with schizophrenia than in control subjects. Potentially consistent with the hypothesis that cellular sequelae of the BDNF Val(66)Met SNP interface with aspects of schizophrenic hippocampal and frontotemporal dysfunction, these results warrant future investigation to understand the contributions of unique patient trait or state variables to these robust interactions.
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DOBA, EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, IZUM, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UILJ, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Prostate cancer (PCa) displays a strong familiarity component and genetic factors; genes regulating inflammation may have a pivotal role in the disease. Epigenetic changes control chromosomal ...integrity, gene functions and ultimately carcinogenesis. The enzyme glycine-N-methyltransferase (GNMT) contributes to S-adenosylmethionine level regulation and, by affecting DNA methylation, influences gene expression. The genotype and allele distribution of single-nucleotide polymorphisms (SNPs) in the promoter regions of vascular endothelial growth factor (VEGF), interleukin (IL)-10, IL-1β, alpha-1-antichymotrypsin (ACT) and GNMT genes, the level of global DNA methylation and the influence of GNMT SNP upon DNA methylation in a PCa case-control study have been investigated.
SNPs of VEGF (rs699947), ACT (rs1884082), IL-1β (rs16944), IL-10 (rs1800896) and GNMT (rs9462856) genes were assessed by PCR or by real-time PCR methods. DNA methylation was assessed by an ELISA assay.
Frequencies of the VEGF AA genotype, the IL-10 A allele and GNMT T allele were higher in PCa. The concomitant presence of the AA genotype of VEGF, the A allele of IL-10 and T allele of GNMT increased the risk of PCa. Total DNA methylation was decreased in PCa; control GNMT T carriers (T+) showed the highest level of DNA methylation.
SNPs in VEGF, IL-10 and GNMT genes might have a synergistic role in the development of PCa. The GNMT T allele may influence PCa risk by affecting DNA methylation and prostate gene expression. Our observations might help implement the screening of unaffected subjects with an increased susceptibility to develop PCa.
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DOBA, EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, IZUM, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UILJ, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Abstract
Background
Heart failure (HF) is one of the leading causes of death from cardiovascular disease. Studies have shown that women have better survival than men, despite the higher number of ...hospitalizations among women. However, little is known about differences in mortality and predictors of death in women and men with heart failure due to ischemic (iCMP) and nonischemic (niCMP) cardiomyopathy.
Purpose
To analyze the mortality and predictors of death in women and men with iCMP and niCMP cardiomyopathy.
Methods
From February 2017 to September 2020, we analyzed mortality and predictors of death in women and men with CHF by iCMP and niCMP. Baseline data included clinical features and echocardiographic findings. Statistical analyses were performed using the Kaplan-Meier (K-M) method and Cox proportional hazards methods to analyze mortality rates in women and men. We used the Score Chi-Square of Cox regression to search for death predictors for women and men.
Results
We studied 7,487 patients, mean age of 64.3 ± 14.2 years, 4,417 (59%) males. Women with iCMP and niCMP had, respectively, higher mean age (p<0.0001), higher mean left ventricular ejection fraction (LVEF) (p<0.001), and smaller left ventricular diastolic diameter (LVDD) (p< 0.001). The mean dose of carvedilol was similar in both genders for iCMP and niCMP. Over a 3-year follow-up period, 420 (15.7%) men and 325 (14.7%) women with niCMP died (p=NS), and in iCMP, 519 (29.8%) men and 211 men died. (24.5%) women (p=0.004). Higher mortality was observed in women with iCMP compared to men with iCMP (p<0.0001). The cumulative incidence of death was higher in men (K-M: log-rank p<0.0001) with iCMP, but similar for niCMP (Figure). Cox regression for death adjusted for age, sex, previous myocardial infarction (MI), diabetes, previous stroke, chronic kidney disease (CKD), atrial fibrillation (AF), HF phenotype (systolic, diastolic, or mildly reduced ejection fraction), and LVEF showed that CKD, AF, diabetes, stroke, LVEF, and age, in descending order of Score Chi-Square, were the main predictors of death for niCMP and CKD, stroke, diabetes, AF, LVEF, age, and MI for iCMP.
Conclusions
Women had a better prognosis than men in iCMP, but similar mortality in niCMP. Gender was not an independent variable of death. Secondary prevention of cardiovascular events from the main predictors of death can significantly reduce the death rate in women and men with CHF by iCMP and niCMP.
A five‐year‐old female cat weighing 3 kg was presented by the owner after noticing a large pink, bilobed mass protruding through the vulva during labour. The cat was in good condition, with ...appropriate lactation, and the newborn kittens were nursing normally. The uterus was not reverted or invaginated at examination, and there was rupture of the mesovarium, mesometrium and uterine‐vaginal connection around the cervix. Manual reduction of the prolapsed uterus was not possible because of torn ligaments. A coeliotomy was performed to remove the ovaries, and the apex of the uterine horns was passed by the vaginal route. The remaining part of the mesometrium was disconnected, and the prolapsed uterus was removed. The queen and kittens were discharged from the hospital on the second day after surgery. An unusual feature of this case is that the prolapse was complete, without eversion of any part of the uterus through a vaginal tear.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Chagas' heart disease is an important public health problem in South America. Several aspects of the pathogenesis are not fully understood, especially in its subclinical phases. On pathology Chagas' ...heart disease is characterized by chronic myocardial inflammation and extensive myocardial fibrosis. The latter has also been demonstrated by late gadolinium enhancement (LGE) by cardiovascular magnetic resonance (CMR). In three clinical phases of this disease, we sought to investigate the presence of LGE, myocardial increase in signal intensity in T2-weighted images (T2W) and in T1-weighted myocardial early gadolinium enhancement (MEGE), previously described CMR surrogates for myocardial fibrosis, myocardial edema and hyperemia, respectively.
Fifty-four patients were analyzed. Sixteen patients with the indeterminate phase (IND), seventeen patients with the cardiac phase with no left ventricular systolic dysfunction (CPND), and twenty-one patients with the cardiac phase with left ventricular systolic dysfunction (CPD). All patients underwent 1.5 T CMR scan including LGE, T2W and MEGE image sequences to evaluate myocardial abnormalities.
Late gadolinium enhancement was present in 72.2 % of all patients, in 12.5 % of IND, 94.1 % of the CPND and 100 % of the CPD patients (p < 0.0001). Myocardial increase in signal intensity in T2-weighted images (T2W) was present in 77.8 % of all patients, in 31.3 % of the IND, 94.1 % of the CPND and 100 % of the CPD patients (p < 0.0001). T1-weighted myocardial early gadolinium enhancement (MEGE) was present in 73.8 % of all patients, in 25.0 % of the IND, 92.3 % of the CPND and 94.1 % of the CPD (p < 0.0001). A good correlation between LGE and T2W was observed (r = 0.72, and p < 0.001).
Increase in T2-weighted (T2W) myocardial signal intensity and T1-weighted myocardial early gadolinium enhancement (MEGE) can be detected by CMR in patients throughout all phases of Chagas' heart disease, including its subclinical presentation (IND). Moreover, those findings were parallel to myocardial fibrosis (LGE) in extent and location and also correlated with the degree of Chagas' heart disease clinical severity. These findings contribute to further the knowledge on pathophysiology of Chagas' heart disease, and might have therapeutic and prognostic usefulness in the future.
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DOBA, GEOZS, IJS, IMTLJ, IZUM, KILJ, KISLJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBJE, UILJ, UKNU, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Precision measurements of solar neutrinos emitted by specific nuclear reaction chains in the Sun are of great interest for developing an improved understanding of star formation and evolution. Given ...the expected neutrino fluxes and known detection reactions, such measurements require detectors capable of collecting neutrino-electron scattering data in exposures on the order of 1 ktonne-yr, with good energy resolution and extremely low background. Two-phase liquid argon time projection chambers (LAr TPCs) are under development for direct Dark Matter WIMP searches, which possess very large sensitive mass, high scintillation light yield, good energy resolution, and good spatial resolution in all three cartesian directions. While enabling Dark Matter searches with sensitivity extending to the ''neutrino floor'' (given by the rate of nuclear recoil events from solar neutrino coherent scattering), such detectors could also enable precision measurements of solar neutrino fluxes using the neutrino-electron elastic scattering events. Modeling results are presented for the cosmogenic and radiogenic backgrounds affecting solar neutrino detection in a 300 tonne (100 tonne fiducial) LAr TPC operating at LNGS depth (3,800 meters of water equivalent). The results show that such a detector could measure the CNO neutrino rate with ∼15% precision, and significantly improve the precision of the {sup 7}Be and pep neutrino rates compared to the currently available results from the Borexino organic liquid scintillator detector.
Aria is a plant hosting a
350
m
cryogenic isotopic distillation column, the tallest ever built, which is being installed in a mine shaft at Carbosulcis S.p.A., Nuraxi-Figus (SU), Italy. Aria is one ...of the pillars of the argon dark-matter search experimental program, lead by the Global Argon Dark Matter Collaboration. It was designed to reduce the isotopic abundance of
39
Ar
in argon extracted from underground sources, called Underground Argon (UAr), which is used for dark-matter searches. Indeed,
39
Ar
is a
β
-emitter of cosmogenic origin, whose activity poses background and pile-up concerns in the detectors. In this paper, we discuss the requirements, design, construction, tests, and projected performance of the plant for the isotopic cryogenic distillation of argon. We also present the successful results of the isotopic cryogenic distillation of nitrogen with a prototype plant.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
A Val(66)Met single-nucleotide polymorphism (SNP) in the brain-derived neurotrophic factor (BDNF) gene impairs activity-dependent BDNF release in cultured hippocampal neurons and predicts impaired ...memory and exaggerated basal hippocampal activity in healthy humans. Several clinical genetic association studies along with multi-modal evidence for hippocampal dysfunction in schizophrenia indirectly suggest a relationship between schizophrenia and genetically determined BDNF function in the hippocampus. To directly test this hypothesized relationship, we studied 47 medication-free patients with schizophrenia or schizoaffective disorder and 74 healthy comparison individuals with genotyping for the Val(66)Met SNP and (15)OH(2)O positron emission tomography (PET) to measure resting and working memory-related hippocampal regional cerebral blood flow (rCBF). In patients, harboring a Met allele was associated with significantly less hippocampal rCBF. This finding was opposite to the genotype effect seen in healthy participants, resulting in a significant diagnosis-by-genotype interaction. Exploratory analyses of interregional resting rCBF covariation revealed a specific and significant diagnosis-by-genotype interaction effect on hippocampal-prefrontal coupling. A diagnosis-by-genotype interaction was also found for working memory-related hippocampal rCBF change, which was uniquely attenuated in Met allele-carrying patients. Thus, both task-independent and task-dependent hippocampal neurophysiology accommodates a Met allelic background differently in patients with schizophrenia than in control subjects. Potentially consistent with the hypothesis that cellular sequelae of the BDNF Val(66)Met SNP interface with aspects of schizophrenic hippocampal and frontotemporal dysfunction, these results warrant future investigation to understand the contributions of unique patient trait or state variables to these robust interactions.
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DOBA, EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, IZUM, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UILJ, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
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