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Peripartum cardiomyopathy is a disease that occurs during or after pregnancy and leads to a significant decline in cardiac function in previously healthy women. Peripartum cardiomyopathy has a varying prevalence among women depending on the part of the world where they live, but it is associated with a significant mortality and morbidity in this population. Therefore, timely diagnosis, treatment, and monitoring of this disease from its onset are of utmost importance. Although many risk factors are associated with the occurrence of peripartum cardiomyopathy, such as conditions of life, age of the woman, nutrient deficiencies, or multiple pregnancies, the exact cause of its onset remains unknown. Advances in research on the genetic associations with cardiomyopathies have provided a wealth of data indicating a possible association with peripartum cardiomyopathy, but due to numerous mutations and data inconsistencies, the exact connection remains unclear. Significant insights into the pathophysiological mechanisms underlying peripartum cardiomyopathy have been provided by the theory of an abnormal 16-kDa prolactin, which may be generated in an oxidative stress environment and lead to vascular and consequently myocardial damage. Recent studies supporting this disease mechanism also include research on the efficacy of bromocriptine (a prolactin synthesis inhibitor) in restoring cardiac function in affected patients. Despite significant progress in the research of this disease, there are still insufficient data on the safety of use of certain drugs treating heart failure during pregnancy and breastfeeding. Considering the metabolic changes that occur in different stages of pregnancy and the postpartum period, determining the correct dosing regimen of medications is of utmost importance not only for better treatment and survival of mothers but also for reducing the risk of toxic effects on the fetus.

Wistar-Kyoto (WKY) rats subjected to chronic mild stress (CMS) represent a valid model of treatment-resistant depression (TRD). Considering that depression is more prevalent in women than in men, in the present study, female rats were used. We investigated the effect of CMS on behavior and different factors involved in neuroinflammatory processes and neuroplasticity in the hippocampus and medial prefrontal cortex (mPFC) of WKY female rats. The results show that unstressed WKY females exhibited hypolocomotion, decreased exploratory behavior, and an increase in the total grooming time. After exposure to CMS, WKY females displayed intensified grooming. To investigate potential neural mechanisms underlying these behavioral changes, we analyzed signaling and inflammatory pathways in the hippocampus and mPFC. The findings indicate reduced BDNF and elevated levels levels of IL-1β in both brain structures and NLRP3 in the mPFC of unstressed WKY female rats. WKY rats subjected to CMS showed a further decrease in BDNF levels and increased IL-1β and NLRP3 in these brain structures. WKY showed reduced pERK1/2 and increased pp38 levels in both brain structures, while CMS revealed a further increase of pp38 in WKY in these brain structures. Expressions of p110β and pAKT were decreased in the hippocampus and mPFC of WKY rats. The CMS further suppressed p110 and the downstream AKT phosphorylation in the hippocampus, but did not affect the p110 and pAKT in the mPFC. Our findings indicate behavioral and molecular differences in genetically vulnerable WKY female rats and in their response to CMS that may be involved in TRD., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Gender differences exist in depression incidence and antidepressant efficacy. In addition to the neurotransmission theory of depression, inflammation and disrupted signaling pathways play crucial roles in the pathophysiology of depression. Endocannabinoids offer a novel approach to treat inflammatory and emotional disorders like depression. URB597, a FAAH inhibitor, reduces endocannabinoids breakdown. In this study, URB597 effects were investigated on the pro-inflammatory cytokine interleukin-1β (IL-1β), nucleotide binding and oligomerization domain-like receptor family pyrin domain-containing 3(NLRP3), and mitogen-activated protein kinase (MAPK)/ phosphatidylinositol 3-hydroxy kinase/ protein kinase B (PI3K) signaling in the hippocampus and the medial prefrontal cortex (mPFC) of male and female rats subjected to chronic unpredictable stress (CUS). The results show that CUS induces depression-like behaviors, and the URB597 exhibited antidepressant-like effects inboth sexes. URB597 reduced the CUS-induced NLRP3 and IL-1β increase in the hippocampus and mPFC of both sexes. URB597 increased the reduced pERK1/2 levels in the mPFC of both sexes and hippocampus of CUS males. URB597 also prevented the increase in p38 phosphorylation after chronic stress in the mPFC of both sexes and in the hippocampus of the females. The CUS suppressed the downstream Akt phosphorylation in the mPFC and hippocampi of both sexes. URB597 produced an up-regulation of the pAkt in the hippocampus of the CUS animals but did not affect the pAkt in the mPFC. These data demonstrated a sexual dimorphism in the neural cell signaling, and in the effects of endocannabinoids, and indicated these dimorphisms are region-specific., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Endocannabinoids act as a stress response system; simultaneously, the modulation of this system has emerged a novel approach for the therapy of cardiovascular disorders. We investigated the protective effects of the chronic administration of the fatty acid amide hydrolase inhibitor URB597 on morphology, pro-inflammatory and anti-inflammatory cytokine, the cytoplasm-nuclear distribution of JAK2/STAT3, and NF-κB and Nrf2/HO-1 signaling in the left ventricle of female and male rats exposed to chronic unpredictable stress. Our results show that URB597 treatment exhibits an antidepressant-like effect, decreases the heart/body weight ratio, prevents the hypertrophy of cardiomyocytes, and reduces the increased level of IL-6 in the wall of the left ventricle of stressed female and male rats. The phosphorylation levels of JAK2 and STAT3 in the ventricle of male rats treated with URB597 were declined, whereas in female rats the decrease of STAT3 was observed. In addition, URB597 reduced increased NF-κB in both females and males and increased the expression of Nrf2 and HO-1 protein in the cytosol of male rats, whereas did not affect their levels in females. Cardioprotective effects of URB597 could be linked to the ability to inhibit the JAK2 in males and the STAT3 inflammatory signaling pathways in both females and males., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Nuts and seeds are an indispensable part of the plant-based diet, which is becoming increasingly popular due to the evidence of their health benefits and contribution to sustainability and planetary health. Since the health effects of consuming nuts and seeds directly depend on their nutritional composition and consumed amount, it is essential to know the exact chemical composition of each nut and seed so that appropriate dietary interventions can be adequately planned. The present study aimed to examine the chemical composition of nuts and seeds obtained from the Serbian market and to highlight the similarities and differences in their nutritional composition. In twenty-four samples of nuts and seeds, the content of total lipids, including fatty acid profile, total proteins, including amino acid profile, total carbohydrates (sugars and fibers), phytosterols, and minerals were determined. Content of selected nutrients in grams (g) or milligrams (mg) of nuts and seeds was expressed in one portion (28 g) and as a percentage of contribution of Reference Intakes (% RI) and Dietary Reference Value (% DRV) for macronutrients and minerals, respectively. Some of the seed representatives appeared to be rich sources of essential omega-3 fatty acid, α-linolenic acid (ALA) (flax seed vs . walnut, 6.50 vs . 0.56 g per portion, respectively), dietary fibers (chia seed vs. raw almond, 10.6 vs. 3.4 g per portion, respectively), calcium (black sesame seed vs . almond roasted, 32.4% NRV vs . 8.1% NRV per portion, respectively), magnesium (hemp seed vs. Brazil nut, 38.3% NRV vs . 27.8% NRV per portion, respectively), and zinc (hemp seed vs. pine nut, 21.4% NRV vs. 17.6% NRV per portion, respectively). Our results highlighted the crucial role of seeds in the diet, especially as a better source of nutrients compared to nuts. Furthermore, it was seen that nuts and seeds are different and complementary in their composition. Thus, in order to meet the needs for certain nutrients for which nuts and seeds are used as dietary sources (essential fatty acids, minerals, dietary fibers), it would be beneficial to combine both nuts and seeds as a part of a healthy dietary pattern., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Dodevska, Kukic Markovic, Sofrenic, Tesevic, Jankovic, Djordjevic and Ivanovic.)

An increasing body of evidence shows significant sex differences in the mammalian brain in multiple behaviours and psychiatric and neurological diseases and as well as that the endocannabinoid system may differ between males and females. In this study we investigated sex differences in working, short-term and long-term memory and the expression of β 2 -adrenergic and D1- and D2-receptors in the mPFC and hippocampus, brain regions that are involved in stress response and memory modulation in rats exposed to the chronic unpredictable stress (CUS) and the potential beneficial effects of the chronic fatty acid amide hydrolase inhibitor URB597 treatment. Chronically stressed male rats had an improvement of working memory, while stressed females showed very low object-recognition abilities. On the other hand, animals of both sexes exhibited long-term memory impairment. Our results showed that CUS decreased the expression of β 2 -adrenoceptors in the mPFC and D1 receptors in the mPFC and hippocampus of male rats and decreased β 2 -adrenoceptors and D1- receptors in the hippocampus of female. URB597 treatment had a positive effect on the short-term memory of stressed animals of both sexes whereas failed to restore long-term memory and did not affect the protein levels β2-adrenoceptors and D1 receptors in the hippocampus of CUS female rats. The present results support that endocannabinoids induced long-term memory and neurochemical alternations which are sex dependent, suggesting sex specific treatment strategies of mental disorders., (Copyright © 2021 Elsevier B.V. All rights reserved.)

The study aimed to discriminate renal allografts with impaired function by measuring cortical renal blood flow (cRBF) using magnetic resonance imaging arterial spin labelling (ASL-MRI) in paediatric and young adult patients. We included 18 subjects and performed ASL-MRI on 1.5 T MRI to calculate cRBF on parameter maps. cRBF was correlated to calculated glomerular filtration rate (GFR) and compared between patient groups with good (GFR ≥ 60 mL/min/1.73 m 2 ) and impaired allograft function (GFR < 60 mL/min/1.73 m 2 ). Mean cRBF in patients with good allograft function was significantly higher than in patients with impaired allograft function (219.89 ± 57.24 mL/min/100 g vs. 146.22 ± 41.84 mL/min/100 g, p < 0.008), showing a highly significant correlation with GFR in all subjects (r = 0.75, p < 0.0001). Also, the diffusion-weighted imaging (DWI-MRI) apparent diffusion coefficient (ADC) and Doppler measurements of peak-systolic and end-diastolic velocities and the resistive index (PS, ED, RI) were performed and both methods showed no significant difference between groups. ADC implied no correlation with GFR (r = 0.198, p = 0.464), while PS indicated moderate correlation to GFR (r = 0.48, p < 0.05), and PS and ED moderate correlation to cRBF (r = 0.58, p < 0.05, r = 0.56, p < 0.05, respectively). Cortical perfusion as non-invasively measured by ASL-MRI differs between patients with good and impaired allograft function and correlates significantly with its function., (© 2022. The Author(s).)

Introduction: The present study examined the effects of fatty acid amide hydrolase inhibitor URB597 on the level of plasma catecholamine and their content, synthesis, and degradation in the adrenal medulla of male and female rats subjected to chronic unpredictable stress (CUS)., Material and Methods: Male and female Wistar rats were exposed to the 6 weeks of CUS and treated intraperitoneally with either 0.3 mg/kg/day of URB597 or vehicle in the last 2 weeks of stress protocol. Catecholamines' plasma levels and catecholamines' levels in adrenal medulla were examined using Elabscience ELISA kits. Western blot analysis was used to detect the protein in the medulla., Results: The results of our experiment showed that adrenal weights and catecholamine of unstressed control were higher in females and that CUS induced further enlargement of adrenal glands and catecholamine content and its synthesis compared to male rats. CUS caused an increase of plasma norepinephrine and depletion of norepinephrine content as well as unchanged synthesis and degradation of catecholamine in the adrenal medulla of male rats. URB597 reduced enlarged adrenals and catecholamine content and its synthesis in stressed female rats. URB597 reduces increased plasma norepinephrine and restores its content in the adrenal medulla, unchanging the expression of enzyme synthesis, while reduced protein levels of monoamine oxidase A in male rats are exposed to CUS., Discussion: Our results support the role of endocannabinoids as an antistress mechanism that inhibits elevated adrenomedullary activation and promotes its recovery to baseline in both male and female stressed rats., (© 2021 S. Karger AG, Basel.)

Sex differences in the susceptibility to chronic unpredictable stress (CUS) and the effects of fatty acid amide hydrolase (FAAH) inhibitor URB597 in rats have been investigated in this study. In this context, we investigated the effects of prolonged treatment with URB597 on behavior, pro-inflammatory interleukin-6 (IL-6) and anti-inflammatory interleukin-10 (IL-10), catecholamine content and the expression of its biosynthetic and degrading enzymes in the hippocampus, hypothalamus and medial prefrontal cortex (mPFC) of rats subjected to CUS. The results show that CUS increases anxiety-like and depression-like behaviors but it was more pronounced in females. The data suggests sex differences in brain cytokines, catecholamines and their enzymes of synthesis and degradation expression in response to CUS. Our findings indicate that the FAAH inhibitor URB597 differently regulated catecholamine levels and its enzymes of synthesis and degradation in the examined brain areas of male and female rats. URB treatment failed to reduce anxiety or restore reduced norepinephrine and did not affect enzymes of catecholamine degradation in the mPFC, hippocampus and hypothalamus of CUS female rats. These studies are important because they investigate the neurochemical consequences of stress related mood disorders that might lead to the development of sex specific treatments., (Copyright © 2020. Published by Elsevier Inc.)

The changes in sympathetic innervations in lymphoid organs could be a key factor in immune dysregulation. The endocannabinoid system has been shown to exhibit potent immunomodulatory effects that may differ between males and females, representing a potential therapeutic target for peripheral and central inflammatory disorders. Thus, in the present study, an examination was made of the effect of fatty acid amide hydrolase inhibitor URB597 treatment on splenic catecholamine content, synthesis, uptake and degradation in chronically unpredictably stressed (CUS) female and male rats. The results show that CUS increases anxiety-like behaviors and that URB597 had an anxiolytic effect on chronically stressed animals of both sexes. CUS induced the expression of plasma interleukin - 6 (IL-6), interleukin - 10 (IL-10) and IL-6 in the spleen, whereas the expression of IL-10 was reduced in the spleen of both sexes. URB597 treatment did not cause changes in IL-6 in plasma or the spleen, whereas it increased IL-10 in the spleen in CUS animals of both sexes. CUS caused a significant depletion of noradrenaline content in the spleen of female rats and a reduction in noradrenaline uptake in the spleen of female rats, while stressed males had a small but insignificant decrease of splenic noradrenaline levels and an enhanced uptake. The FAAH inhibitor URB597 enhances reduced noradrenaline content, affecting its uptake directly at the level of the spleen. It gives rise to the possibility that endocannabinoids exert a neurorestorative effect on the sympathetic nerve system and cell-mediated immune responses in the spleen of chronically stressed rats., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Baseline sympathetic activity was found to be elevated in rheumatoid arthritis (RA) patients and it is related to increased cardiovascular risk in these patients. Although many studies have highlighted the association between RA and increased cardiac sympathetic activity, the underlying mechanistic links remain unclear. The aim of the present study was to understand how diseases-triggered changes in gene expression may result in maladaptive physiological changes. Our results suggest that the equilibrium between noradrenaline synthesis, release and reuptake was disrupted in the ventricles of arthritic rats. In the acute phase of the arthritic process, decreased gene expression of MAO-A might lead to accumulation of noradrenaline in myocardial interstitial space, whereas increased gene expression of NET protected cardiomyocytes from the deleterious effects of enhanced noradrenaline. During the chronic phase, reduced expression of β 1 -adrenoceptor and decreased efficiency of noradrenaline reuptake contribute to progressive damage of the myocardium and limits heart efficiency., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Some patients with unstable angina and critical stenosis of the left anterior descending coronary artery (LAD) present with Wellens syndrome (WS), i.e., inverted or biphasic T-waves in the anterior precordial leads. We assessed clinical, angiographic, electro- and echocardiographic characteristic of patients with WS. In this retrospective study, clinical, angiographic, electro- and echocardiographic characteristic of 35 patients with WS were compared to 57 patients with critical LAD stenosis and normal resting electrocardiogram (ECG), and 45 subjects with normal coronary angiogram. QTc dispersion was measured from the 12-lead ECG as the difference between longest and shortest QTc intervals. Mechanical dispersion was defined as the time difference between the longest and shortest contraction durations which were measured as the time from the first deflection of the QRS complex to maximum myocardial shortening of each 18 segmental longitudinal strain curves derived by speckle tracking echocardiography. There were no significant differences in the complexity and location of the LAD lesion, anterograde and collateral flow in LAD and coronary artery dominance between patients with WS and normal ECG (P > 0.05, for all). Patients with WS had lower global longitudinal strain (GLS) and more pronounced both QTc and myocardial mechanical dispersion than patients with critical LAD stenosis and normal ECG, and control subjects (P < 0.05). T-wave changes in patients with WS are associated with more profound regional myocardial dysfunction and increased QTc and myocardial mechanical dispersion. Similar angiographic characteristics of the LAD lesion were seen in patients with WS and normal ECG.

Objective: After radioiodine therapy of differentiated thyroid cancer (DTC) patients, whole body scintigraphy (WBS) is standard procedure before releasing the patient from the hospital. A common problem is the precise localization of regions where the iod-avide tissue is located. Sometimes is practically impossible to perform precise topographic localization of such regions., Method: In order to face this problem, we have developed a low-cost Vision-Fusion system for web-camera image acquisition simultaneously with routine scintigraphic whole body acquisition including the algorithm for fusion of images given from both cameras. For image acquisition in the gamma part of the spectra we used e.cam dual head gamma camera (Siemens, Erlangen, Germany) in WBS modality, with matrix size of 256×1024 pixels and bed speed of 6cm/min, equipped with high energy collimator. For optical image acquisition in visible part of spectra we have used web-camera model C905 (Logitech, USA) with Carl Zeiss® optics, native resolution 1600×1200 pixels, 34 o field of view, 30g weight, with autofocus option turned "off" and auto white balance turned "on". Web camera is connected to upper head of gamma camera (GC) by a holder of lightweight aluminum rod and a plexiglas adapter. Our own Vision-Fusion software for image acquisition and coregistration was developed using NI LabVIEW programming environment 2015 (National Instruments, Texas, USA) and two additional LabVIEW modules: NI Vision Acquisition Software (VAS) and NI Vision Development Module (VDM). Vision acquisition software enables communication and control between laptop computer and web-camera. Vision development module is image processing library used for image preprocessing and fusion. Software starts the web-camera image acquisition before starting image acquisition on GC and stops it when GC completes the acquisition. Web-camera is in continuous acquisition mode with frame rate f depending on speed of patient bed movement v (f=v/∆ cm , where ∆ cm is a displacement step that can be changed in Settings option of Vision-Fusion software; by default, ∆ cm is set to 1cm corresponding to ∆ p =15 pixels). All images captured while patient's bed is moving are processed. Movement of patient's bed is checked using cross-correlation of two successive images. After each image capturing, algorithm extracts the central region of interest (ROI) of the image, with the same width as captured image (1600 pixels) and the height that is equal to the ∆ p displacement in pixels. All extracted central ROI are placed next to each other in the overall whole-body image. Stacking of narrow central ROI introduces negligible distortion in the overall whole-body image. The first step for fusion of the scintigram and the optical image was determination of spatial transformation between them. We have made an experiment with two markers (point radioactivity sources of 99m Tc pertechnetate 1MBq) visible in both images (WBS and optical) to find transformation of coordinates between images. The distance between point markers is used for spatial coregistration of the gamma and optical images. At the end of coregistration process, gamma image is rescaled in spatial domain and added to the optical image (green or red channel, amplification changeable from user interface)., Subjects: We tested our system for 10 patients with DTC who received radioiodine therapy (8 women and two men, with average age of 50.10±12.26 years). Five patients received 5.55Gbq, three 3.70GBq and two 1.85GBq. Whole-body scintigraphy and optical image acquisition were performed 72 hours after application of radioiodine therapy., Conclusion: Based on our first results during clinical testing of our system, we can conclude that our system can improve diagnostic possibility of whole body scintigraphy to detect thyroid remnant tissue in patients with DTC after radioiodine therapy.

Aims: Ischaemic but viable myocardium may exhibit prolongation of contraction and QT interval duration, but it is largely unknown whether non-invasive assessment of regional heterogeneities of myocardial deformation and QT interval duration could identify patients with significant coronary artery disease (CAD)., Methods and Results: We retrospectively studied 205 patients with suspected CAD who underwent coronary angiography. QTc dispersion was assessed from a 12-lead electrocardiogram (ECG) as the difference between the longest and shortest QTc intervals. Contraction duration was assessed as time from the ECG R-(Q-)wave to peak longitudinal strain in each of 18 left ventricular segments. Mechanical dispersion was defined as either the standard deviation of 18 time intervals (dispersionSD18) or as the difference between the longest and shortest time intervals (dispersiondelta). Longitudinal strain was measured by speckle tracking echocardiography. Mean contraction duration was longer in patients with significant CAD compared with control subjects (428 ± 51 vs. 410 ± 40 ms; P = 0.032), and it was correlated to QTc interval duration (r = 0.47; P < 0.001). In contrast to QTc interval duration and dispersion, both parameters of mechanical dispersion were independently associated with CAD (P < 0.001) and had incremental value over traditional risk factors, wall motion abnormalities, and global longitudinal strain (GLS) for the detection of significant CAD., Conclusion: The QTc interval and myocardial contraction duration are related to the presence of significant CAD in patients without a history of previous myocardial infarction. Myocardial mechanical dispersion has an incremental value to GLS for identifying patients with significant CAD., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2015. For permissions please email: journals.permissions@oup.com.)

Purpose: The objectives of the study were to use the International Atomic Energy Agency (IAEA) software package for the analysis of scintigraphic renal dynamic studies to obtain values of curve parameters and excretory parameters in children with hydronephrosis and to validate the reliability of these numerical outputs by comparing with values established by consensus reports., Patients and Methods: Fifty children with hydronephrosis (median age, 16 months; 30 boys, 20 girls; 99 kidneys) underwent Tc-MAG3 diuresis renography. Studies were analyzed by 2 observers, and according to the assessment of images, renograms, and differential function, kidneys were classified as normal (42, kidneys contralateral to hydronephrotic kidney), hypotonic unobstructed (49), and obstructed (8). The IAEA software was applied to each renogram. The parameters analyzed were as follows: normalized residual activity at 20 minutes (NORA 20) and on postmicturition (PM) acquisition, output efficiency at 20 minute (OE 20), PM to maximum renal count ratio (PM/max), and mean transit time (MTT)., Results: Mean values for normal, hypotonic unobstructed, and obstructed kidneys were as follows: NORA 20: 0.25, 0.57, and 2.16; OE 20 (%): 94.5, 87, and 57; normalized residual activity on PM acquisition: 0.02, 0.03, and 0.27; PM/max: 0.01, 0.02, and 0.13; and MTT (minutes): 1.9, 3.5, and 8.9, respectively. Difference between obstruction/dilatation and normal/dilatation was significant (P < 0.0001), as well as the correlation between NORA 20/OE 20 (R = -0.982). Cutoff values to predict obstruction were as follows: NORA 20, 1.6; OE 20, 73%; NORA PM, 0.11; PM/max, 0.06; and MTT, 8.23 minutes., Conclusions: The IAEA software package gives reliable values of numerical parameters of renal excretion. The use of the software improves diagnostic accuracy of diuresis renography in children.