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Background: Late failure of arterial aortocoronary conduits may result from abnormal activity of cells found in the vessel wall, including macrophages. The purpose of this study was to assess if there are any associations between the number of macrophages and overexpression of matrix metalloproteinases (MMPs) in the wall of arterial grafts, as well as their clinical significance. Methods: This study involved 128 consecutive patients with a mean age of 64.9 ± 9.7 years who underwent elective surgery for coronary artery disease (CAD). The surplus segments of internal thoracic artery (ITA) and radial arteries (RA) were taken for immunohistochemical analysis of macrophage numbers and MMPs expression. The participants who reached the clinical primary end-point (cardiacrelated death, acute coronary syndrome or progression of CAD) had a follow-up angiography. Results: The mean numbers of macrophages were higher on RA (70 [24; 112]) than ITA cross-sections (44 [24; 59]; p < 0.001). Median expression of both MMP2 and MMP9 were stronger in the ITA than RA cross-sections (p < 0.001). A significant positive correlation of MMP2 expression and a number of macrophages infiltrating the tunica media of arterial segments were noted on both ITA and RA cross-sections. In addition, the arterial segments of the 6 patients who reached clinical end-point had higher numbers of macrophages and stronger MMP2 expression when compared to the rest of the participants. Conclusions: Macrophage infiltration of arterial wall grafts prior to harvesting may be associated with higher risk of late occlusion and MMP2 might be facilitating this process.

Our study aimed to explore the association between serum C-reactive protein (CRP) and post-stroke depressive symptoms. We prospectively recruited 572 patients with ischemic stroke or transient ischemic attack in whom serum CRP level was measured within 48 h after stroke onset. Depressive symptoms were assessed at day 8 and 3 months after stroke in 405 and 306 patients, respectively. Patients with greater depressive symptoms at day 8 and patients with greater depressive symptoms 3 months after stroke had higher CRP level (median: 7.9 vs 4.3 mg/L, P 9.2 mg/L was associated with depressive symptoms at day 8 (OR: 2.06, 95%CI: 1.30–3.28, P 4.3 mg/L was associated with depressive symptoms 3 months after stroke (OR: 1.79, 95%CI: 1.06–3.02, P = 0.03). In the multivariate analysis, higher CRP level was related to depressive symptoms at day 8 (OR: 2.23, 95%CI: 1.28–3.90, P

Macrophages, detected as CD68+ cells, are considered to have marked contribution to aorto-coronary grafts disease. The purpose of this study was to find any ultrastructural differences in CD68+ cells between arterial and venous aorto-coronary grafts. The surplus segments of radial artery (RA) and saphenous vein (SV) were obtained from 50 patients with the mean age of 63.4±9.2 years who undergo elective coronary artery bypass grafting (CABG). The vascular segments were analyzed by means of both light (to assess number and distribution of macrophages within their walls) and transmission electron microscopy (to evaluate ultrastructure of CD68+ cells in the vessel layers). Histological analysis revealed that not only more macrophages (median (25th; 75th percentile)) were found on the transverse sections of veins (95 (67; 135)) than arteries (66 (43; 108)) (p Ultrastructural characteristics of both forms of macrophages infiltrating wall of aorto-coronary grafts is similar irrespective of the vessel type. More active cells in the inner layers of the venous conduits may contribute to their inferior outcomes compared to the arteries. Running title: Macrophages and aorto-coronary grafts

U dzieci narażonych na szkodliwe działanie alkoholu w okresie prenatalnym często po urodzeniu występują różnego rodzaju zaburzenia. W wyniku teratogennego wpływu alkoholu wypijanego przez matkę w czasie ciąży przebieg rozwoju różnych kompetencji u dziecka jest zaburzony. Jedną z bardzo istotnych dla prawidłowego funkcjonowania społecznego jest teoria umysłu. Niniejszy artykuł prezentuje przegląd aktualnych wyników badań naukowych poświęconych występującym u dzieci z FASD deficytom w rozwoju teorii umysłu. Opracowany przegląd nie pozwala na wyprowadzenie spójnego modelu istniejącego związku, gdyż opublikowane w literaturze badania są nieliczne i mają pewne ograniczenia. Zatem postuluje się dalsze badania nad deficytami w rozwoju teorii umysłu występującymi u dzieci z FASD w kontekście modelu opracowanego przez Barona-Cohena, których wstępny projekt został zarysowany.

In this study, the lingonberry fruit extract (LGBE) has been investigated for the ability to suppress the inflammatory response and mitigate oxidative stress in activated 3T3-L1 adipocytes and RAW 264.7 macrophages. The obtained results showed that LGBE significantly reduced IL-6, MCP-1 and IL-1β production, and counteracted the decrease in adiponectin and IL-10 expression in TNF-α-induced adipocytes. Moreover, LGBE exhibited a high anti-inflammatory potential in the macrophage cell culture by down-regulation the expression of pro-inflammatory mediators (IL-6, TNF-α, IL-1β, MCP-1, COX-2, iNOS). Furthermore, LGBE decreased intracellular ROS generation in inflamed adipocytes by enhancing expression of antioxidant defense enzymes (SOD, catalase, GPx) and inhibiting an oxidant enzyme (NADPH oxidase 4), which is one of the primary sources of ROS. In conclusion, we have demonstrated that lingonberry fruit may reduce adipose tissue inflammation and support immune cell homeostasis, and thus can be considered a natural tool for inflammation control.

In patients with diabetes, functional changes in microcirculation and subclinical vascular pathology precede clinical manifestation of microangiopathic complications. The objective of this study was to evaluate the association between established vascular risk factors and density, maturity, and reactivity of dermal blood vessels in adults with type 1 diabetes (DM1). We included 148 DM1 patients (87 men) with a median (IQR) age of 40.5 (30.5–49) years and a median diabetes duration of 21 (17–29.5) years. The control group consisted of 13 healthy volunteers (6 men) with a median (IQR) age of 36 (31–43). Accumulation of advanced glycation end products (AGEs) was assessed using the AGE-Reader device. In the immunohistochemical (IHC) analyses, anti-CD133, anti-CD34, anti-CD31, and anti-vWF autoantibodies were used. Microvessel density (MVD) in the skin was calculated using the “hot spots technique”. Microvascular function was examined by single-point laser-Doppler flowmetry (LDF). Median MVD, calculated for both papillary and reticular dermis, for CD31 antigen expression was 38 (19–56) per 1 mm2. The median CD34+ blood vessel density was 121 (100–155) per 1 mm2, CD133+ was 79 (63–92) per 1 mm2, and vWF+ was 50 (40–69) per 1 mm2. The average CD34/CD31 index was 2.78, the vWF/CD31 ratio was 1.32 and the CD133/CD31 ratio was 1.75. The CD34/CD31 index was positively associated with serum triglyceride concentration (Beta: 0.26, p = 0.012) and negatively associated with serum HDL cholesterol concentration (Beta: −0.22, p = 0.027), both independently from age, sex, diabetes duration, BMI, HbA1c value, presence of hypertension, and eGFR. We found a negative correlation between MVD assessed by CD31 and skin AF (r = −0.21, p = 0.016). In LDF, the area under the blood flow/time curve (AUC) correlated positively with CD31+ MVD (r = 0.21, p = 0.011) and negatively with CD34+ MVD (r = −0.20, p = 0.017). The MVD did not differ between participants with diabetes and healthy controls, and it did not differ according to the presence of retinopathy among the participants with diabetes. Atherogenic dyslipidemia is associated with increased formation of new blood vessels, characterized by high expression of CD34 and low reactivity in LDF. Conversely, chronic hyperglycemia and excessive formation of AGEs may result in decreased vascularity.

Berries, especially members of the Ericaceae family, are among the best dietary sources of bioactive compounds with beneficial health effects. The most popular berries are in the genus Vaccinium, such as bilberry (Vaccinium myrtillus), cranberry (Vaccinium macrocarpon, V. oxycoccos), and blueberry (Vaccinium corymbosum). Lingonberry (Vaccinium vitis-idaea) is less prevalent in the daily human diet because they are collected from the wild, and plant breeding of lingonberry is still on a small scale. Lingonberries are classed as “superfruits” with the highest content of antioxidants among berries and a broad range of health-promoting effects. Many studies showed various beneficial effects of lingonberries, such as anti-inflammatory, antioxidant, and anticancer activities. Lingonberries have been shown to prevent low-grade inflammation and diet-induced obesity in diabetic animals. Moreover, lingonberry intake has been associated with a beneficial effect on preventing and treating brain aging and neurodegenerative disorders. The consumption of berries and their health-promoting activity is a subject receiving a great deal of attention. Many studies investigated the natural compounds found in berries to combat diseases and promote healthy aging. This article’s scope is to indicate the potential beneficial effect of lingonberry consumption on health, to promote well-being and longevity.

Background Fetal alcohol spectrum disorders (FASD) is a group of conditions resulting from prenatal alcohol exposure (PAE). Patients with FASD experience a variety of neuropsychological symptoms resulting from central nervous system impairment. Little is known about sleep disorders associated with PAE. The objective of this study was to investigate sleep problems related to FASD. Methods Forty patients (median age 8 years (6; 11)) diagnosed with FASD and forty typically developing children (median age 10 years (8; 13)) were recruited for the 1st phase of the study. In the 1st phase, the screening of sleep problems was performed with Child Sleep Habit Questionnaire (CSHQ) filled in by a caregiver. Those of the FASD group who scored above 41 points were qualified to the 2nd phase of the study and had an in-lab attended polysomnography (PSG) performed. The measurements consisted of electroencephalogram, electrooculograms, chin and tibial electromyogram, electrocardiogram, ventilatory monitoring, breathing effort, pulse oximetry, snoring and body position. Their results were compared to PSG laboratory reference data. Results The number of participants with sleep disturbances was markedly higher in the FASD group as compared to typically developing children (55% vs. 20%). The age-adjusted odds ratio for a positive result in CSHQ was 4.31 (95% CI: 1.54–12.11; p = 0.005) for FASD patients as compared to the control group. Significant differences between the FASD as compared to the typically developing children were observed in the following subscales: sleep onset delay, night wakings, parasomnias, sleep disordered breathing, and daytime sleepiness. Children from the FASD group who underwent PSG experienced more arousals during the sleep as compared with the PSG laboratory reference data. The respiratory indices in FASD group appear higher than previously published data from typically developing children. Conclusion The results support the clinical observation that sleep disorders appear to be an important health problem in individuals with FASD. In particular distorted sleep architecture and apneic/hypopneic events need further attention.

Oxidative stress and dysregulated adipocytokine secretion accompanying hypertrophied adipose tissue induce chronic inflammation, which leads to vascular endothelial dysfunction. The present study investigated the ability of anthocyanin (ACN) and non-anthocyanin polyphenol (PP) fractions from lingonberry fruit to mitigate adipose tissue hypertrophy and endothelial dysfunction using 3T3-L1 adipocytes and human umbilical vein endothelial cells (HUVECs). This study showed that the PP fraction decreased intracellular ROS generation in hypertrophied adipocytes by enhancing antioxidant enzyme expression (SOD2) and inhibiting oxidant enzyme expression (NOX4, iNOS). Moreover, PP and ACN fractions reduced triglyceride content in adipocytes accompanied by downregulation of the expression of lipogenic genes such as aP2, FAS, and DAGT1. Treatment with both fractions modulated the mRNA expression and protein secretion of key adipokines in hypertrophied adipocytes. Expression and secretion of leptin and adiponectin were, respectively, down- and upregulated. Furthermore, PP and ACN fractions alleviated the inflammatory response in TNF-α-induced HUVECs by inhibiting the expression of pro-inflammatory genes (IL-6, IL-1β) and adhesion molecules (VCAM-1, ICAM-1, SELE). The obtained results suggest that consuming polyphenol-rich lingonberry fruit may help prevent and treat obesity and endothelial dysfunction due to their antioxidant and anti-inflammatory actions.

Objectives Apathy after stroke is common and has a negative impact on functional recovery. Neuroimaging correlates of poststroke apathy remain unclear. We aimed to investigate microstructural changes associated with the severity of poststroke apathy symptoms. Methods We assessed 67 patients with cerebral ischaemia who underwent magnetisation transfer brain imaging 12-15 months after stroke. We used magnetisation transfer ratio (MTR) to represent microstructural integrity. We performed whole-brain voxel-based analysis and subsequent region of interest analysis to investigate the association between MTR and symptoms of poststroke apathy. To assess apathy symptoms, we used clinician-reported version of the Apathy Evaluation Scale. Results Voxel-based analysis showed the association between symptoms of apathy and decreased MTR in areas overlapping with structures located in both hemispheres: left thalamus, bilateral hippocampus, bilateral fornix/stria terminalis, right amygdala, splenium of the corpus callosum, the retrolenticular part of left internal capsule and left sagittal stratum. In the region of interest analysis, only lower MTR in right fornix/stria terminalis was associated with greater poststroke apathy symptoms in a multivariate logistic model (odds ratio: 1.25, 95% CI: 1.09-1.46, p = 0.003). These associations were independent of depressive symptoms. Conclusion Magnetisation transfer brain imaging 12-15 months after stroke revealed changes in microstructural integrity associated with apathy symptoms in brain areas related to processing emotional information and reward valuation.

BackgroundFetal alcohol spectrum disorders (FASD) is a group of conditions resulting from prenatal alcohol exposure (PAE). Patients with FASD experience a variety of neuropsychological symptoms resulting from central nervous system impairment. Little is known about sleep disorders associated with PAE. The objective of this study was to investigate the prevalence and characterize sleep problems among individuals with FASD.Methods40 patients from FASD diagnostic center (median age 8 years (6; 11)) diagnosed with one of the FASD diagnosis and 40 patients from the control group (median age 10 years (8; 13)) participated in the study. In the 1st phase, the screening of sleep problems was performed with Child Sleep Habit Questionnaire (CSHQ) filled in by a caregiver. Those who scored above 41 points were qualified to the 2nd phase of the study in which in-lab attended polysomnography (PSG) was performed. The measurements consisted of electroencephalographic channels, left and right electrooculograms, chin electromyogram, left and right tibialis electromyogram, electrocardiogram, ventilatory monitoring, breathing effort, pulse oximetry, snoring and body position.ResultsThe number of participants with sleep disturbances was markedly higher in the study group as compared to controls (55% vs. 20%). The age-adjusted odds ratio for a positive result in CSHQ was 4.31 (95% CI: 1.54-12.11; p=0.005) for FASD patients as compared to the control group. Significant differences between the study and control groups were observed in the following subscales: sleep onset delay, night wakings , parasomnias , sleep disordered breathing, and daytime sleepiness. In PSG children from the FASD group and children from the control group experienced more arousals during the sleep than the children from the laboratory control group. ). There were no significant differences in comparison of respiratory indexes between FASD and control groups although indices in both groups were higher than previously published data for a normal population.ConclusionSleep disorders are more common among individuals with FASD than among healthy children. As distorted sleep can affect daily performance and worsen neurodevelopmental issues, it is vital for the pediatricians and other FASD specialists to include the question about sleep in the anamnesis.

Post-stroke depression (PSD) is the most frequent neuropsychiatric consequence of stroke. The nature of the relationship between PSD and mortality still remains unknown. One hypothesis is that PSD could be more frequent in those patients who are more vulnerable to physical disability, a mediator variable for higher level of physical damage related to higher risk of mortality. Therefore, the authors&rsquo, objective was to explore the assumption that PSD increases disability after stroke, and secondly, that mortality is higher among patients with PSD regardless of stroke severity and other neuropsychiatric conditions. We included 524 consecutive patients with acute stroke or transient ischemic attack, who were screened for depression between 7&ndash, 10 days after stroke onset. Physical impairment and death were the outcomes measures at evaluation check points three and 12 months post-stroke. PSD independently increased the level of disability three (OR = 1.94, 95% CI 1.31&ndash, 2.87, p = 0.001), and 12 months post-stroke (OR = 1.61, 95% CI 1.14&ndash, 2.48, p = 0.009). PSD was also an independent risk factor for death three (OR = 5.68, 95% CI 1.58&ndash, 20.37, p = 0.008) and 12 months after stroke (OR = 4.53, 95% CI 2.06&ndash, 9.94, p = 0.001). Our study shows the negative impact of early PSD on the level of disability and survival rates during first year after stroke and supports the assumption that depression may act as an independent mediator for disability leading to death in patients who are more vulnerable for brain injury.

To explore the role of systemic inflammation in post-stroke delirium, we investigated the level of two inflammatory mediators: high mobility group box 1 (HMGB1) and galectin-3 binding protein (Gal-3BP). Of 571 stroke patients, we compared plasma levels of HMGB1 and Gal-3BP in 79 delirious patients with 81 non-delirious patients matched for age and stroke severity. Delirious patients had higher Gal-3BP level (median: 1440 vs 1053 ng/mL, P < 0.01). An elevated level of Gal-3BP was associated with an increased risk of delirium. HMGB1 levels did not differ between groups. Our results suggest that pro-inflammatory monocytes and macrophages might be involved in delirium pathophysiology.

Granulosa cells (GCs) have many functions and are fundamental for both folliculogenesis and oogenesis, releasing hormones and communicating directly with the oocyte. Long-term in vitro cultures of GCs show significant stem-like characteristics. In the current study, RNA of human ovarian granulosa cells was collected at 1, 7, 15 and 30 days of long-term in vitro culture. Understanding the process of differentiation of GCs towards different cell lineages, as well as the molecular pathways underlying these mechanisms, is fundamental to revealing other possible stemness markers of this type of cell. Identifying new markers of GC plasticity may help to understand the aetiology and recurrence of a wide variety of diseases and health conditions and reveal possible clinical applications of the ovarian tissue cells, affecting not only the reproductive ability but also sex hormone production. Granulosa cells were the subject of this study, as they are readily available as remnant material leftover after in vitro fertilisation procedures and exhibit significant stem-like characteristics in culture. The change in gene expression was investigated through a range of molecular and bioinformatic analyses. Expression microarrays were used, allowing the identification of groups of genes typical of specific cellular pathways. This candidate gene study focused on ontological groups associated with muscle cell morphogenesis, structure, development and differentiation, namely, “muscle cell development”, “muscle cell differentiation”, “muscle contraction”, “muscle organ development”, “muscle organ morphogenesis”, “muscle structure development”, “muscle system process” and “muscle tissue development”. The results showed that the 10 most upregulated genes were keratin 19, oxytocin receptor, connective tissue growth factor, nexilin, myosin light chain kinase, cysteine and glycine-rich protein 3, caveolin 1, actin, activating transcription factor 3 and tropomyosin, while the 10 most downregulated consisted of epiregulin, prostaglandin-endoperoxide synthase 2, transforming growth factor, interleukin, collagen, 5-hydroxytryptmine, interleukin 4, phosphodiesterase, wingless-type MMTV integration site family and SRY-box 9. Moreover, ultrastructural observations showing heterogeneity of granulosa cell population are presented in the study. At least two morphologically different subpopulations were identified: large, light coloured and small, darker cells. The expression of genes belonging to the mentioned ontological groups suggest the potential ability of GCs to differentiate and proliferate toward muscle lineage, showing possible application in muscle regeneration and the treatment of different diseases.

Background: Stroke patients are particularly vulnerable to delirium episodes, but very little is known about its subsequent adverse mental health outcomes. The author’s objective was to explore the association between in-hospital delirium and depression, anxiety, anger and apathy after stroke. Methods: A total of 750 consecutive patients with acute stroke or transient ischemic attack, were screened for delirium during hospitalization. Patients underwent mental health evaluation in hospital, 3 and 12 months post-stroke; depression, apathy, anxiety and anger were the outcomes measured at all evaluation check points. Results: Delirium was an independent risk factor for depression (OR = 2.28, 95%CI 1.15–4.51, p = 0.017) and aggression (OR = 3.39, 95%CI 1.48–7.73, p = 0.004) at the hospital, for anxiety 3 months post-stroke (OR = 2.83, 95%CI 1.25–6.39, p = 0.012), and for apathy at the hospital (OR = 4.82, 95%CI 2.25–10.47, p < 0.001), after 3 (OR = 3.84, 95%CI 1.31–11.21, p = 0.014) and 12 months (OR = 4.95, 95%CI 1.68–14.54, p = 0.004) post stroke. Conclusions: The results of this study confirm, that mental health problems are very frequent complications of stroke. Delirium in the acute phase of stroke influences mental health of patients. This effect is especially significant in the first months post-stroke and vanishes with time, which suggests that in-hospital delirium might not be a damaging occurrence in most measures of mental health problems from a long-term perspective.

In this paper, we explore the strategy increasingly used to improve the bioavailability of poorly water-soluble crystalline drugs by formulating their amorphous solid dispersions. We focus on the potential application of a low molecular weight excipient octaacetyl-maltose (acMAL) to prepare physically stable amorphous solid dispersions with ibuprofen (IBU) aimed at enhancing water solubility of the drug compared to that of its crystalline counterpart. We thoroughly investigate global and local molecular dynamics, thermal properties, and physical stability of the IBU+acMAL binary systems by using broadband dielectric spectroscopy and differential scanning calorimetry as well as test their water solubility and dissolution rate. The obtained results are extensively discussed by analyzing several factors considered to affect the physical stability of amorphous systems, including those related to the global mobility, such as plasticization/antiplasticization effects, the activation energy, fragility parameter, and the number of dynamically correlated molecules as well as specific intermolecular interactions like hydrogen bonds, supporting the latter by density functional theory calculations. The observations made for the IBU+acMAL binary systems and drawn recommendations give a better insight into our understanding of molecular mechanisms governing the physical stability of amorphous solid dispersions.

Background: Previous research confirmed association between delirium and subsequent dementia in different clinical settings, but the impact of post-stroke delirium on cognitive functioning is still under-investigated. Therefore, we aimed to assess the risk of dementia among patients with stroke and in-hospital delirium. Methods: A total of 750 consecutive patients admitted to the stroke unit with acute stroke or transient ischemic attacks were screened for delirium, during the first seven days after admission. At the three- and twelve-month follow-up, patients underwent cognitive evaluation. The DSM-5 definition for dementia was used. Cases with pre-stroke dementia were excluded from the analysis. Results: Out of 691 included cases, 423 (61.22%) and 451 (65.27%) underwent cognitive evaluation, three and twelve months after stroke; 121 (28.61%) and 151 (33.48%) patients were diagnosed with dementia, respectively. Six (4.96%) patients with dementia, three months post-stroke did not meet the diagnostic criteria for dementia nine months later. After twelve months, 37 (24.50%) patients were diagnosed with dementia, first time after stroke. Delirium in hospital was an independent risk factor for dementia after three months (OR = 7.267, 95%CI 2.182–24.207, p = 0.001) but not twelve months after the stroke. Conclusions: Patients with stroke complicated by in-hospital delirium are at a higher risk for dementia at three but not twelve months post-stroke.

Pregnancy and tobacco smoking (TS) each can cause increases in reactive oxygen species (ROS) production; this, in turn, can lead to disorders in iron management and disruption of the pro- and anti-oxidant balance. The aim of the study was to analyze the influence of TS and Cd on Fe, Zn, and anti-oxidant levels (i.e. glutathione [GSH], metallothionein [MT]) in the blood of pregnant women. The study reported here evaluated 110 blood samples from pregnant women in their 1st, 2nd and 3rd trimester. Concentrations of ferritin and transferrin were measured in the serum; Zn, Fe and cotinine in the plasma, that of Cd in whole blood, that for glutathione in red blood cell lysates, and levels of metallothionein both in the plasma and in lysates prepared from isolated erythrocytes. The results indicated there was a decrease in Zn and increase in Cd and metallothionein levels in pregnant women smokers as compared to in nonsmoking counterparts. Differences in intracellular MT concentration were noted both in smoking and nonsmoking women during pregnancy while there were no changes in extracellular MT level. A decline in circulating ferritin and a rise in transferrin during pregnancy was observed in all groups. Based on the results, it was concluded that exposure to TS-associated xenobiotics like Cd could result in higher MT levels in erythrocytes and in pregnant smokers, the major anti-oxidant mechanism that is in place is one being mediated by MT and not by reduced GSH.

Pregnancy complicated by preeclampsia (PE) and intrauterine growth restriction (IUGR) promotes endothelial cell (EC) dysfunction. Our in vitro study aimed to evaluate the endothelial cell morphology after acute and chronic exposition to medium supplemented with serum taken from healthy pregnant women and women with IUGR and IUGR with PE. In the same condition, ECs viability, proliferation, reactive oxygen species (ROS) production, and serum concentration of vascular endothelial growth factor (VEGF) were also measured. Pregnant women with IUGR and IUGR with PE-delivered babies with reduced body mass and were characterized in elevated blood pressure, urine protein loss, and reduced level of VEGF. The 24 hours of exposition did not exert any morphological changes in ECs, except the reduction in cell viability, but prolonged exposition resulted in significant morphological changes concerning mostly the swelling of mitochondria with accompanying ROS production, cell autophagy, reduced cell viability, and proliferation only in complicated pregnancies. In conclusion, the sera taken from women with IUGR and IUGR with PE show a detrimental effect on ECs, reducing their viability, proliferation, and generating oxidative stress due to dysfunctional mitochondria. This multidirectional effect might have an adverse impact on the cardiovascular system in women with IUGR and PE.

Granulosa cells (GCs) are a population of somatic cells whose role after ovulation is progesterone production. GCs were collected from patients undergoing controlled ovarian stimulation during an in vitro fertilization procedure, and they were maintained for 1, 7, 15, and 30 days of in vitro primary culture before collection for further gene expression analysis. A study of genes involved in the biological processes of interest was carried out using expression microarrays. To validate the obtained results, Reverse Transcription quantitative Polymerase Chain Reaction (RT-qPCR) was performed. The direction of changes in the expression of the selected genes was confirmed in most of the examples. Six ontological groups (“cell cycle arrest”, “cell cycle process”, “mitotic spindle organization”, “mitotic spindle assembly checkpoint”, “mitotic spindle assembly”, and “mitotic spindle checkpoint”) were analyzed in this study. The results of the microarrays obtained by us allowed us to identify two groups of genes whose expressions were the most upregulated (FAM64A, ANLN, TOP2A, CTGF, CEP55, BIRC5, PRC1, DLGAP5, GAS6, and NDRG1) and the most downregulated (EREG, PID1, INHA, RHOU, CXCL8, SEPT6, EPGN, RDX, WNT5A, and EZH2) during the culture. The cellular ultrastructure showed the presence of structures characteristic of mitotic cell division: a centrosome surrounded by a pericentric matrix, a microtubule system, and a mitotic spindle connected to chromosomes. The main goal of the study was to identify the genes involved in mitotic division and to identify the cellular ultrastructure of GCs in a long-term in vitro culture. All of the genes in these groups were subjected to downstream analysis, and their function and relation to the ovarian environment are discussed. The obtained results suggest that long-term in vitro cultivation of GCs may lead to their differentiation toward another cell type, including cells with cancer-like characteristics.

Oxidative stress and inflammation in hypertrophied adipose tissue with excessive fat accumulation play a crucial role in the development of obesity and accompanying metabolic dysfunctions. This study demonstrated the capacity of elderberry fruit (EDB) extract to decrease the elevated production of reactive oxygen species in hypertrophied 3T3-L1 adipocytes. Treatment with the EDB extract resulted in modulation of mRNA expression and protein secretion of key adipokines in hypertrophied adipocytes. Expression of leptin and adiponectin was, respectively, down- and up-regulated. Moreover, glucose uptake stimulation was noticed in mature adipocytes, both sensitive to insulin and insulin resistant. This may suggest a positive effect of EDB extract on insulin resistance status. The extract was also found to alleviate the inflammatory response in activated RAW 264.7 macrophages by down-regulating the expression of proinflammatory genes (TNF-&alpha, IL-6, COX-2, iNOS) and suppressing the enhanced production of inflammatory mediators (TNF-&alpha, IL-6, PGE2, NO). In vitro experiments showed that the EDB extract could inhibit digestive enzymes, including &alpha, amylase, &alpha, glucosidase, and pancreatic lipase, leading to reduced intestinal absorption of dietary lipids and carbohydrates. Further in vivo studies could be postulated to support EDB as a functional food component for the prevention and treatment of obesity and metabolic-immune comorbidities.

Blackcurrant fruits are a rich source of polyphenolic compounds with high antioxidant capacity and potent anti-inflammatory properties. In this study, blackcurrant extract digested in an artificial gastrointestinal tract and its intestinal permeable fraction were investigated for their ability to suppress inflammatory responses induced in a two-component cell culture system of intestinal epithelial cells and macrophages. The obtained results showed the capacity of the extract at a concentration of 1 mg of freeze-dried blackcurrant powder per mL to down-regulate the expression of inflammatory mediators, such as IL-8 (54 ± 7%) and COX-2 (17 ± 6%) in intestinal cells and IL-1α (76 ± 4%), IL-1β (91 ± 2%), and IL-6 (61 ± 5%) in macrophages stimulated with lipopolysaccharides. Inhibited COX-2 (44 ± 6%) and iNOS (15 ± 7%) expression played a role in reducing the production of prostaglandin E2 (40 ± 20%) and NO (31 ± 9%), respectively. Decreased TNF-α secretion (24 ± 5%) by activated macrophages was also observed...

Background and purpose Delirium is a very common neurobehavioral complication after stroke, but its influence on long-term outcome is not well characterized. The objective of the study was to determine the prognostic significance of delirium for functional status, nursing home admission, and mortality in a large cohort of patients with delirium in the acute phase of stroke assessed 3 and 12 months after stroke. Methods All stroke survivors included in PROPOLIS were followed up (n = 682). Outcome data included: discharge destination, recurrence of stroke, cardiovascular complications, functional activity and mobility, nursing home admission, and mortality. Results Patients with delirium were discharged to another hospital or nursing home significantly more often than those presenting without delirium. The 3- and 12-month post-stroke mortality rates were higher in delirious patients (OR 6.41 CI 3.76–10.92; p

Although delirium is the most common neurobehavioral complication after stroke, its motor subtypes-hypoactive, hyperactive, mixed, and none-as well as their risk factors are not well characterized. Motor subtypes influence recognition and prognosis of delirium in hospitalized patients.The aim of this prospective study was to assess the frequency of poststroke delirium subtypes and to describe their predictive models. Consecutive patients with stroke were screened for delirium with the Confusion Assessment Method for the Intensive Care Unit. Delirium was diagnosed according to DSM-5 criteria, and subtypes were classified with the Delirium Motor Subtype Scale-4. Baseline demographic characteristics, biochemistry, stroke-related data, medications, neurological deficits, and premorbid cognitive and functional impairments were assessed.Out of 750 patients (mean age, 71.75 years [SD=13.13]), 203 (27.07%) had delirium: 85 (11.34%) were hypoactive, 77 (10.27%) were mixed hypoactive-hyperactive, 31 (4.13%) were hyperactive, and 10 (1.33%) had an unspecified type. Cognitive impairment at the time of hospital admission and spatial neglect, among other factors, were identified as the best predictors for all motor delirium subtypes.Screening for poststroke delirium is important because the hypoactive subtype bears the worst prognosis and is misdiagnosed the most compared with other subtypes. All identified factors for the predictive models of delirium subtypes are routinely assessed during hospital admission. Their occurrence in patients with stroke should alert the treating physician to the high risk for a particular delirium subtype.

Solar photo-Fenton process in raceway pond reactors was investigated at neutral pH as a sustainable tertiary treatment of real urban wastewater. In particular, the effect on antibiotic resistance determinants was evaluated. An effective inactivation of different wild bacterial populations was achieved considering total and cefotaxime resistant bacteria. The detection limit (1 CFU mL−1) was achieved in the range 80–100 min (5.4–6.7 kJ L−1 of cumulative solar energy required) for Total Coliforms (TC) (40–60 min for resistant TC, 4.3–5.2 kJ L−1), 60–80 min (4.5–5.4 kJ L−1) for Escherichia coli (E. coli) (40 min for resistant E. coli, 4.1–4.7 kJ L−1) and 40–60 min (3.9–4.5 kJ L−1) for Enterococcus sp. (Entero) (30–40 min for resistant Entero, 3.2–3.8 kJ L−1) with 20 mg L−1 Fe2+ and 50 mg L−1 H2O2. Under these mild oxidation conditions, 7 out of the 10 detected antibiotics were effectively removed (60–100%). As the removal of antibiotic resistance genes (ARGs) is of concern, no conclusive results were obtained, as sulfonamide resistance gene was reduced to some extent (relative abundance

Endometriosis represents an often painful, estrogen-dependent gynecological disorder, defined by the existence of endometrial glands and stroma exterior to the uterine cavity. The disease provides a wide range of symptoms and affects women’s quality of life and reproductive functions. Despite research efforts and extensive investigations, this disease’s pathogenesis and molecular basis remain unclear. Conventional endometriosis treatment implies surgical resection, hormonal therapies, and treatment with nonsteroidal anti-inflammatory drugs, but their efficacy is currently limited due to many side effects. Therefore, exploring complementary and alternative therapy strategies, minimizing the current treatments’ adverse effects, is needed. Plants are sources of bioactive compounds that demonstrate broad-spectrum health-promoting effects and interact with molecular targets associated with endometriosis, such as cell proliferation, apoptosis, invasiveness, inflammation, oxidative stress, and angiogenesis. Anti-endometriotic properties are exhibited mainly by polyphenols, which can exert a potent phytoestrogen effect, modulating estrogen activity. The available evidence derived from preclinical research and several clinical studies indicates that natural biologically active compounds represent promising candidates for developing novel strategies in endometriosis management. The purpose of this review is to provide a comprehensive overview of polyphenols and their properties valuable for natural treatment strategy by interacting with different cellular and molecular targets involved in endometriosis progression.

The aim of the study was to evaluate the impact of early pregnancy and exposure to tobacco smoke on antioxidant status and copper, zinc, and cadmium concentrations in the blood of non-smoking and smoking, as well as non-pregnant or pregnant women. The study included 213 women. More specifically, 150 women in first trimester of pregnancy and 63 non-pregnant women. Women were divided into subgroups according to exposure to tobacco smoke. Pregnancy significant influences higher copper and lower zinc concentration in the serum, whereas exposure to tobacco smoke during pregnancy is mainly associated with an elevation in cadmium and zinc concentration. It seems that metallothionein, superoxide dismutase, and glutathione peroxidase are the important antioxidants during early pregnancy, when exposure to tobacco smoke occurs, whereas the pregnancy itself is associated with a higher concentration of metallothionein and activity of catalase. Both pregnancy in the first trimester and exposure to tobacco smoke decrease glutathione concentration. In addition, active and passive maternal smoking have a similarly negative effect on antioxidant status in the first trimester. Early pregnancy as well as exposure to tobacco smoke is associated with significant alteration in antioxidant status and copper, zinc, and cadmium concentration. Due to a small number of smoking subjects (11 cases of non-pregnant, active smokers and 14 pregnant active smokers), the obtained results should be treated as a pilot, and this should be considered for future studies.

INTRODUCTION Advanced glycation end products (AGEs) play a crucial role in the pathogenesis of diabetic peripheral neuropathy (DPN). OBJECTIVES The aim of the study was to assess the skin accumulation of AGEs in patients with long‑lasting type 1 diabetes in relation to the presence of DPN. PATIENTS AND METHODS We evaluated 178 patients with type 1 diabetes (99 men; age, 43 years [interquartile range [IQR], 34-54 years]; disease duration, 25 years [IQR, 18-31 years]). DPN was diagnosed if 2 or more of the following 5 abnormalities were present: symptoms of neuropathy, lack of ankle reflexes, and impaired sensation of touch, temperature, and/or vibration. PGP 9.5‑immunoreactive nerve fibers were counted to assess intraepidermal nerve fiber density (IENFD) in skin biopsy. The accumulation of AGEs in the skin was assessed on the basis of skin autofluorescence (AF). RESULTS Patients with DPN (45%), compared with those without neuropathy, had higher skin AF (2.6 AU [IQR, 2.3-3.1 AU] vs 2.1 AU [IQR, 1.8-2.5 AU]; P

The aim of the study was to analyze the effects of oral contraceptives (OCs) on pro/antioxidant status in the blood of healthy women aged 20-25 years. Individuals were divided into OCs users and OCs nonusers. Markers of oxidative stress in the blood such as Cu, Cu/Zn ratio, malondialdehyde (MDA), glutathione oxidized (GSSG), and gamma-glutamyl transpeptidase (GGT) were determined. Antioxidants such as glutathione reduced (GSH), catalase (CAT), glutathione reductase (GR), glutathione peroxidase (GPx), glutathione S-transferase (GST), and superoxide dismutase (SOD) were estimated. Higher Cu concentrations, Cu/Zn ratio and GGT activity in women taking OCs were noted. A significant increase in MDA concentrations in oral OCs users was observed. Heightened activity of CAT in plasma was observed in OCs users, whereas SOD activity remained unchanged in plasma and erythrocyte lysate. A decline of GSH and GSSG in whole blood and glutathiono-dependent enzymes (GPx in plasma, GR in plasma and GST in lysate) was shown. Use of OCs leads to a pro/antioxidant imbalance. The results in the present study confirmed that GGT is an early marker of oxidative stress. Catalase is the main antioxidant, involved in the removal of free radicals in OCs users.

The environmental occurrence of antimicrobial pharmaceuticals and antibiotic resistant bacteria and antibiotic resistant genes has become a global phenomenon and a multifaceted threat. Integrated actions of many parties are needed to prevent further aggravation of the problem. Well-directed actions require clear understanding of the problem, which can be ensured by frequent revaluation of the existing knowledge and disseminating it among relevant audiences. The goal of this review paper is to discuss the occurrence and abundance of antimicrobial pharmaceuticals in the aquatic environment in context of adverse effects caused directly by these substances and the threat associated with the antibiotics resistance phenomenon. Several classes of antimicrobial pharmaceuticals (aminoglycosides, β-lactams, glycopeptides, macrolides, fluoroquinolones, sulfonamides and trimethoprim, tetracyclines) have been selected to illustrate their sources, environmental abundance, degradation routes (transformation products) and environmental implications including their ecotoxic effect and the spread of antibiotic resistance within the compartments of the aquatic environment and wastewater treatment plants. Wastewater treatment plants are indeed the main source responsible for the prevalence of these factors in the aquatic environment, since predominantly the plants have not been designed to retain antimicrobial pharmaceuticals. In order to limit the prevalence of these impurities into the environment, better source control is recommended as well as the establishment of stricter environmental quality standards. Counteracting all the above-mentioned threats requires to undertake integrated activities based on cooperation of professionals and scientists from various fields of science or industry, such as environmental sciences, medicine, veterinary, pharmacology, chemical engineering and others.

Background: An imbalance in activity between matrix metalloproteinases (MMPs), particularly gelatinases, and tissue inhibitors (TIMPs) is considered as one of the mechanisms leading to aortocoronary graft failure. Aim: To assess variability of gelatinase expression in the walls of aortocoronary conduits and to check its impact on coronary artery bypass graft (CABG) outcomes. Methods: This study involved 101 consecutive patients (61 men and 40 women) who underwent CABG. An immunohistochemical analysis of MMP2, MMP9, TIMP1 and TIMP2 expression was performed on the cross-sections of internal thoracic artery (ITA), radial artery (RA) and saphenous vein (SV). The histological findings concerning patients who had occluding lesions in SV grafts (SVGD(+) group) were compared to the remainders (SVGD(-) group). Results: Median expression of both MMPs and TIMPs was the weakest in the ITA wall. MMP expression in the RA and SV cross-sections was comparable (RA=SV) whereas expression of TIMPs was stronger in the RA than SV wall (RA>SV). In the majority of the SV segments, but not in the arteries, MMP immunostaining intensity was comparable or stronger than TIMPs. In the veins harvested from SVGD(+) individuals, tissue expression of both MMPs was more pronounced than in SVGD(-) subjects. In the same time, TIMP levels were found to be comparable. Conclusions: Tissue imbalance in metalloproteinase-to-inhibitor expression in the wall of vessels might predispose to graft failure. Stronger expression of tissue inhibitors than gelatinases in the arterial grafts might be the explanation of the favorable long-term outcomes.

Delirium is the most common and serious neurobehavioral complication in acute hospital admissions. Some patients develop signs of delirium but do not meet all diagnostic criteria. Stroke is a major risk factor for delirium. The aim of this prospective study was to build a predictive model for delirium and subsyndromal post-stroke delirium. Patients with stroke were screened for delirium during the first 7 days after admission. Delirium was diagnosed according to DSM-V criteria. Baseline demographic, biochemical, stroke-related data, medications used, neurological deficit, and premorbid cognitive and functional impairment were assessed. 750 consecutive stroke patients (71.75 ± 13.13 years) were recruited; 203 (27.07%) had delirium. In predictive model for delirium MoCA score and white blood count on admission, neglect, vision deficits, physical impairment, and higher comorbidity prior to stroke had the highest predictive value. Subsyndromal delirium was diagnosed in 60 patients. MoCA score and potassium level on admission, and urinary tract infection during hospitalization had the highest predictive value for its development. Delirium occurs in one-fourth of admissions due to stroke; subsyndromal delirium is less prevalent and affects less than one per ten patients. The hyperactive form is the most rare type of delirium. The factors best predicting delirium are easily assessed in everyday practice and their co-occurrence in patients with stroke should alert the treating physician of high risk of delirium.

Background Experimental studies suggest that systemic inflammation contributes to the pathophysiology of delirium. The aim of our study was to determine blood-derived inflammatory signatures of post-stroke delirium. Methods We included 144 ischemic stroke patients. We assessed delirium on a daily basis during the first 7 days of hospitalization. Venous blood was collected at day 3 after the onset of stroke and stimulated ex vivo with lipopolysaccharide (LPS). We measured LPS-induced cytokine concentration (TNFα, IP-10, IL-1β, IL-6, IL-8, IL-10, and IL-12p70) as well as plasma levels of IL-6 and TNFα. Results Delirium was diagnosed in 21.5% of patients. After correction for monocyte count, patients with delirium had reduced LPS-induced TNFα, IP-10, IL-1β, IL-6, and IL-12 release. The plasma IL-6 level was higher in delirious patients compared to patients without delirium. After adjusting for stroke severity and infections, higher ex vivo TNFα (OR 0.29, 95%CI 0.11–0.72, P = 0.01), IP-10 (OR 0.25, 95%CI 0.08–0.73, P = 0.01), IL-1β (OR 0.42, 95%CI 0.20–0.89, P = 0.02), and IL-12 (OR 0.07, 95%CI 0.01–0.70, P = 0.02) release was associated with the reduced risk of delirium. In multivariate analysis, the higher plasma IL-6 was associated with the increased risk of delirium (OR 1.61, 95%CI 1.00–2.58, P = 0.04). Conclusions Reduced ex vivo release of pro-inflammatory cytokines after LPS stimulation and the elevated plasma IL-6 are signatures of post-stroke delirium.

Background and aims The immune response to acute cerebral ischemia plays an important role in the pathophysiology of stroke and could be a therapeutic target. Toll-like receptor 4 (TLR4) is a master regulator of innate immunity. The aim of our study was to determine the association between selected cytokine release after TLR4 activation in blood cells and the outcome after ischemic stroke. Methods We included 156 ischemic stroke patients (median age: 69; 40.4% female). Venous blood was collected at day 3 after the onset of stroke and stimulated ex vivo with lipopolysaccharide (LPS). The LPS-induced level of tumor necrosis factor alpha (TNFα) was used as a proxy of the MyD88-dependent pathway, and interferon-gamma-inducible protein 10 (IP-10) was used as a proxy of the MyD88-independent pathway. The functional outcome was assessed at 3 months after stroke onset. Results TNFα (median: 2.2 vs. 3.5 pg/103 monocytes, p Conclusions The reduced release of TNFα and IP-10 after ex vivo blood stimulation with endotoxin is independently associated with poor outcome after stroke. Our results suggest that the inhibition of both the MyD88-dependent pathway and MyD88-independent pathway of TLR4 signaling in blood cells correlates with an unfavorable prognosis in stroke patients.

In order to evaluate potential therapeutic properties of Sambucus nigra fruit extract, its anti-inflammatory effects were investigated in lipopolysaccharide-activated RAW264.7 macrophages. Physiochemical changes in the extract composition, which occur following oral administration, were mimicked in an artificial alimentary tract, while transepithelial absorption was simulated using enterocyte-like Caco-2 cell monolayer, imitating intestinal barrier. The obtained results showed that gastrointestinal digested extract, transported across intestinal epithelium, down-regulated the expression of major genes of inflammatory pathway, such as IL-1β, IL-6, TNF-α and COX-2. Reduction of IL-6, TNF-α and prostaglandin E2 secretion was also observed as a result of LPS-stimulated macrophages' treatment. Moreover, enhanced nitric oxide production in response to inflammatory stimuli in RAW264.7 cells was controlled by the digested and intestinal permeable fraction of elderberry extract.

The concentration of metallothionein (MT), a low-molecular-weight protein, is regulated by many factors, primarily metals (zinc, cadmium, copper), cytokines, glucocorticoides and free radicals. These factors are determined by such aspects of human biology as gender, pregnancy and age, as well as by environmental factors including the use of oral contraceptives and cigarette smoking, all which may affect MT levels in the body. The aim of this study was to investigate the influence of these biological and environmental factors on MT concentrations in erythrocyte lysate and in plasma. MT concentrations were determined by a two-step direct enzyme-linked immunosorbent assay. Evaluation of exposure to cigarette smoking was performed by checking cotinine levels in the plasma of subjects. The studies showed higher MT concentrations in both the erythrocyte lysate and plasma of women when compared to men. Furthermore, pregnancy causes an increase of MT concentration in plasma, while oral contraceptives cause an elevated concentration of MT in erythrocyte lysate. Age impacts plasma MT concentrations in men, whereas it does not affect concentrations of MT in erythrocyte lysate.

BACKGROUND: The aim of the study was to verify the influence of oral contraceptives (OCs) on lipid profile and the arylesterase lactonase and phosphotriesterase activities of paraoxonase 1 (PON1). Also commonly hepatic enzymes: aspartate aminotransferase (AST) alanine aminotransferase (ALT) and gamma-glutamyltranspherase (GGT) were measured. METHODS: Lipid profile and hepatic enzymes were determined using commercial available reagents. Paraoxonase activities were estimated using earlier published procedures. Blood samples were collected from 120 women of similar age (22.6+/-1.0 years) with similar BMI (20.71+/-2.20 kg/m2 ). Participations were divided into two groups: 74 females do not take (group A) and 46 women taking OCs (group B). RESULTS: Higher triglycerides and lower low-density lipoproteins levels were observed in group B than in group A) (56.9+/-19.7 mg/dL. Castelli risk index I was significantly higher in group B when compared to group A (P

The ability to decode emotions in amyotrophic lateral sclerosis (ALS) and fronto-temporal dementia (FTD) still requires research. The evidence demonstrates impairment of emotion recognition in behavioral variant FTD (bvFTD); data regarding emotions decoding in ALS are discrepant. Ability to decode emotions may depend on different variables, among them executive functions. The aim of this study is to compare patients with bvFTD, ALS and controls on emotions decoding ability. The second aim was to explore correlation between executive impairment and emotional decoding abilities. This study contained 26 patients with bvFTD, 42 with ALS and 31 control subjects with the same age, education and disease severity. Patients completed neuropsychological tests, and emotional recognition tasks. Patients with bvFTD decoded emotions worse than ALS and controls. More significant associations between the ability to decode emotions and executive dysfunction were found in ALS than in bvFTD patients and controls.

BACKGROUND Broccoli is a common vegetable recognized as a rich source of antioxidants. To date, research on the antioxidant properties of broccoli, predominantly conducted on extracts, has not considered the lesions of composition and this activity after gastrointestinal digestion. Here the stability of antioxidants during gastrointestinal digestion was evaluated in conjunction with the protective effects of broccoli sprouts (BS) against oxidative stress in human colon cells. RESULTS The obtained data suggest that, among the biocompounds identified in BS, glucosinolates were mainly degraded under gastrointestinal digestion, while phenolics, particularly hydroxycinnamic acid derivatives, were the most resistant constituents. The antioxidant capacity of BS extract subjected to gastrointestinal digestion was similar to or higher than that determined for non-digested BS. Gastrointestinal digested BS extract exhibited reactive oxygen species (ROS)-inhibitory capacity in NCM460 human colon cells, with 1 mg mL−1 showing an ROS clearance of 76.59%. A 57.33% reduction in oxidative DNA damage in NCM460 cells due to treatment with digested BS extract was observed. CONCLUSION The results lend support to the possible application of BS as a rich source of antioxidants to improve the defensive system against oxidative stress in the human colon mucosa. © 2014 Society of Chemical Industry

The purpose of this work was to compare glutathione status in the blood of women taking oral contraceptives, female smokers and preg- nant women using both the capillary electrophoresis (CE) and alloxan methods. The studies were performed on the whole blood prepared by deproteinization by 25% metaphosphoric acid. The reduced gluta- thione (GSH) was measured by alloxan and CE methods. Oxidized glu- tathione (GSSG) was measured by CE and the GSH/GSSG ratio was calculated. In pregnant women (Group A), women taking oral contra- ceptives (Group B) and female smokers (Group C), lower concentra- tions of GSH were observed compared with the control group (Group D) as measured by CE and alloxan methods, suggesting the presence of oxidative stress. The level of GSSG in Group C was higher than in Group D, indicating glutathione oxidation. In Groups A and B, reduced levels of GSSG were observed, which indicates that other processes be- sides oxidation affect glutathione status. In Groups A and C, a lower GSH/GSSG ratio was observed than in Group D, while in Group B no statistical change was observed. In conclusion, the advantage of CE is the possibility of measuring GSSG, which could allow for a more ac- curate interpretation of the status of GSH in the human body. Oxidation of glutathione in female smokers was indicated, while in pregnant women and women taking oral contraceptives processes other than ox- idation can be associated with a decrease in glutathione levels.

Cranberries (Oxycoccus quadripetalus) are a valuable source of bioactive substances with high antioxidant potential and well documented beneficial health properties. In the present study, the activity of cranberries, in terms of the inhibiting effects of adipogenesis, was investigated using the 3T3-L1 cell line. The obtained results showed that cranberries reduced proliferation and viability of 3T3-L1 preadipocytes in a dose-dependent manner. Treatment with cranberries decreased the number of adipocytes and reduced lipid accumulation in maturing 3T3-L1 preadipocytes, demonstrating an inhibitory effect on lipogenesis. Moreover, it was found that cranberries directly induced lipolysis in adipocytes and down-regulated the expression of major transcription factors of the adipogenesis pathway, such as PPARγ, C/EBPα and SREBP1. These findings indicate that cranberries are capable of suppressing adipogenesis and therefore they seem to be natural bioactive factors effective in adipose tissue mass modulation.

Excessive fat accumulation in hypertrophied adipocytes lead to chronic inflammation, oxidative stress and dysregulated adipokines secretion. In this study, we investigated the ability of raspberry fruit extract (RBE) to mitigate adipose tissue dysfunction using hypertrophied 3T3-L1 adipocytes. The obtained results showed that RBE decreased intracellular ROS generation in hypertrophied adipocytes by enhancing expression of antioxidant defense enzymes SOD, catalase, and GPx, and inhibiting an oxidant enzyme NADPH oxidase 4. Moreover, RBE reduced lipid accumulation accompanied by increased lipid mobilization. RBE significantly inhibited LPL, aP2, FAS and PLIN mRNA expression, and enhanced the expression of HSL. Furthermore, RBE exhibited a high anti-inflammatory potential by down-regulation the expression of pro-inflammatory mediators (IL-6, TNF-α, IL-1β, MCP-1 and leptin), and counteracted the decrease in adiponectin and IL-10 expression. Raspberry fruit could be potentially valuable dietary ingredient towards mitigating adverse metabolic consequences of fat cell hypertrophy, thus reducing the risk of metabolic disorders.

Delirium is a transient condition characterized by sudden and fluctuating disturbances in cognitive function. The condition can be considered a sign of the brain's vulnerability and diminished resilience to insult. Among the many clinical manifestations are cognitive, psychomotor, and sleep disturbances. Delirium is associated with longer hospital stays, worse functional outcomes, and higher mortality. Although up to 48% of patients who have had a stroke develop delirium, the condition has been studied much less in these patients than in general medicine, surgical, and intensive care patients. Coexisting neurologic deficits in patients with stroke limit the use of screening tools that are widely accepted in other populations. The variability of reported assessment methods highlights the need for delirium screening guidelines in stroke. Further, risk factors that are specific to stroke may play an important role in the etiology of delirium, along with such well-known factors as older age and infections. The delirium literature lacks data on differences in clinical manifestations and course in the various types of stroke. Here we review predisposing factors, diagnostic methods, and biomarkers of delirium in stroke and discuss aspects that need further research.

Atherosclerosis commonly affects the arteries harvested from patients 70 years of age or older. Saphenous vein grafts appear to maintain a higher patency rate after coronary artery bypass grafting in these subjects. The infiltration of macrophages is an early step in saphenous vein graft atherosclerosis; however, little is known regarding the underlying mechanisms of infiltration. The objective of the present report is to evaluate the presence of CD68-positive cells in the saphenous vein wall and correlate initial CD68-positive infiltration to specific clinical and biochemical parameters and the graft patency rate as estimated in patients undergoing coronary artery bypass grafting. A total of 309 patients were allocated into two groups: A1 patients, who were between 50 and 70 years of age, and A2 patients, who were 70 years or older at the time of vein harvesting. CD68 expression was evaluated by immunohistochemistry. There were no significant differences between A1 and A2 patients regarding macrophage expression within any of the analyzed vascular regions. Saphenous vein macrophages were never present in the tunica intima unless they were also expressed in the media or the adventitia. The patients with CD68-positive cells in the tunica intima had a significantly higher number of bypass stenoses when compared with the subjects who did not have CD68-positive cells in this layer. These findings suggest that the CD68-positive cells (those that have not yet developed into foam cells) present in the intima of saphenous vein grafts might serve as a very early marker of graft occlusion.