Zobrazení zdroje stránky Thomsenchurch7931

Effects of natural stressors such as copper (Cu2+), temperature, hypoxia, chloroform and adrenaline on physiological and biochemical responses were investigated in the Mediterranean green crab Carcinus aestuarii from tidal shallow waters of Narta Lagoon, Albania. For this purpose, hemolymph glucose levels, total and differential hemocyte count, in normal and eye-stalked individuals, exposed to above mentioned stressors like, were assessed. In addition, lysosomal membrane stability was evaluated as biomarker of hemocyte toxicity, with possible implications on crab immune response. Hemolymph glucose levels were significantly increased in all treatment groups with 1.25-to 3.5-fold above baseline levels of 37.8&nbsp;±&nbsp;2.7 mgdL-1. Response times were being manifested within 30-120&nbsp;min following exposure and recovery happened within 2&nbsp;h of restoration of pretreatment conditions. Total hemocyte count (THC) and differential hemocyte count (DCH) showed a significant decrease for all stressors, except for copper, were an increase of semi-granular hemocyte fraction were recorded. Meanwhile, significant reduction of neutral red retention time (NRRT), in both eyestalk-ablated and exposed animals, were recorded, indicated the loss of hemocyte lysosomal membrane integrity. The responsiveness of hemolymph blood levels to all stressors, the decrease in total hemocyte count, as well as the loss of lysosomal membrane integrity demonstrated that exposure to environmentally realistic stressors placed a heavy metabolic load on C. aestuarii, modulating their immune competence and overall physiological wellness. Overall, results suggest that monitoring cellular and biochemical parameters like hemolymph glucose titres, TCH, DHC and NRRT, may be useful and sensitive means of evaluating the crustacean's ability to cope with the wide variety of environmental stressors through modulation of the immune parameters. Published by Elsevier Inc.Cherubism is a rare genetic disorder caused primarily by mutations in SH3BP2 resulting in excessive bone resorption and fibrous tissue overgrowth in the lower portions of the face. Bone marrow derived cell cultures derived from a murine model of cherubism display poor osteogenesis and spontaneous osteoclast formation. To develop a deeper understanding for the potential underlying mechanisms contributing to these phenotypes in mice, we compared global gene expression changes in hematopoietic and mesenchymal cell populations between cherubism and wild type mice. In the hematopoietic population, not surprisingly, upregulated genes were significantly enriched for functions related to osteoclastogenesis. However, these upregulated genes were also significantly enriched for functions associated with inflammation including arachidonic acid/prostaglandin signaling, regulators of coagulation and autoinflammation, extracellular matrix remodeling, and chemokine expression. In the mesenchymal population, we observed down regulation of osteoblast and adventitial reticular cell marker genes. Regulators of BMP and Wnt pathway associated genes showed numerous changes in gene expression, likely implicating the down regulation of BMP signaling and possibly the activation of certain Wnt pathways. Analyses of the cherubism derived mesenchymal population also revealed interesting changes in gene expression related to inflammation including the expression of distinct granzymes, chemokines, and sulfotransferases. These studies reveal complex changes in gene expression elicited from a cherubic mutation in Sh3bp2 that are informative to the mechanisms responding to inflammatory stimuli and repressing osteogenesis. The outcomes of this work are likely to have relevance not only to cherubism, but other inflammatory conditions impacting the skeleton. BACKGROUND CD14 is a membrane glycoprotein primarily expressed by myeloid cells that plays a key role in inflammation. Soluble CD14 (sCD14) levels carry a poor prognosis in chronic heart failure (HF), but whether elevations in sCD14 precede HF is unknown. We tested the hypothesis that sCD14 is associated with HF incidence and its subtypes independent of major inflammatory biomarkers among older adults. METHODS AND RESULTS We included participants in the Cardiovascular Health Study without preexisting HF and available baseline sCD14. We evaluated the associations of sCD14, high-sensitivity C-reactive protein (hsCRP), interleukin-6 (IL-6), and white blood cell count (WBC) with incident HF and subtypes using Cox regression. Among 5217 participants, 1878 had incident HF over 13.6 years (609 classifiable as preserved [HFpEF] and 419 as reduced ejection fraction [HFrEF]). After adjusting for clinical and laboratory covariates, sCD14 was significantly associated with incident HF (HR 1.56 per doubling, 95% CI 1.29-1.89), an association that was numerically stronger than for hsCRP (HR per doubling 1.10, 95% CI 1.06-1.15), IL-6 (HR 1.18, 95% CI 1.10-1.25), and WBC (HR 1.24, 95% CI 1.09-1.42), and that remained significant after adjustment for the other markers of inflammation. This association for sCD14 was observed with HFpEF (HR 1.50, 95% CI 1.07-2.10) but not HFrEF (HR 0.99, 95% CI 0.67-1.49). CONCLUSIONS Plasma sCD14 was associated with incident HF independently and numerically more strongly than other major inflammatory markers. This association was only observed with HFpEF in the subset with classifiable HF subtypes. Pending replication, these findings have potentially important therapeutic implications. OBJECTIVES In patients with reduced kidney function there are no established guidelines to suggest combined heart-kidney transplant (HKTx) versus sequential kidney transplant (SKTx) using preoperative value of estimated glomerular filtration (eGFR). METHODS The United Network for Organ Sharing database was queried from 2000 to 2015 to evaluate survival of HKTx and SKTX population stratified by preoperative eGFR rate less then 45ml/min. Aim of the study was to assess the eGFR rate that is most beneficial to perform a concomitant or a sequential kidney transplantation at time of transplant evaluation. RESULTS In our analysis, patients that required SKTx are recipients that, after heart transplantation, developed or worsened kidney insufficiency due to calcineurin inhibitor nephrotoxicity. [https://www.selleckchem.com/products/ly2835219.html LY2835219] In recipients with eGFR less then 30 or dialysis, a total of 545 received HKTx and 80 received SKTx. The median waiting time between heart and kidney transplant in SKTx group was 6 years. The overall post transplant survival was 81% and 80% and 75% and 59% at 5 and 1 years for the HKTx and SKTx groups, respectively (p=0.04). In recipients with eGFR from 30 to 44, a total of 107 received HKTx and 112 received SKTx. The median waiting time between heart and kidney transplant in SKTx group was 4 years. Overall post transplant survival showed no statistically significant differences in HKTx group (n=107) compared to SKTx group (n=112) and was 90% and 95% at 1 year and 74% and 52% at 5 years, respectively (p=0.4) . CONCLUSIONS In order to optimize organ and patient survival, eGFR value can be utilized to discern between HKTx versus SKTx in patients with decreased renal function at the time of heart transplantation. Patients with eGFR less then 30 or in dialysis presented better survival with HKTx, while both SKTx and HTKx are suitable for patients with eGFR between 30 and 45. BACKGROUND Iron deficiency (ID) is common in patients with chronic heart failure (CHF), but the underlying causes are not fully understood. We investigated if ID is associated with decreased iron absorption in patients with CHF. METHODS AND RESULTS We performed an oral iron absorption test in 30 patients and 12 controls. The patients had CHF with reduced (n=15) or preserved (n=15) ejection fraction and ID defined as S-Ferritin less then 100 µg/L, or S-Ferritin 100-299 µg/L and transferrin saturation less then 20%. The controls had no HF or ID and were of similar age and gender. Blood samples were taken before, and two hours after ingestion of 100 mg ferroglycin sulphate. The primary endpoint was the delta plasma (P) iron at two hours. The delta P-iron was higher in the HF group than in the control group (median increase 83.8 [61.5;128.5] µg/dL in HF vs 47.5 [30.7;61.5] µg/dL in controls, p=0.001), indicating increased iron absorption. There was no significant difference between the HFrEF and HFpEF groups (p=0.46). CONCLUSION We found increased iron absorption in CHF patients with ID compared to controls without ID and HF, indicating that reduced iron absorption is not a primary cause of the high prevalence of ID in CHF patients. CLINICAL TRIAL REGISTRATION EudraCT 2017-000158-21. OBJECTIVE To assess the association between aspirin use and risk of aneurysmal subarachnoid hemorrhage (aSAH). METHODS A systematic search was performed in various databases updated on Oct. 22, 2019. link2 The heterogeneity test was performed for each outcome variable. Random-effect model and fixed-effect model were respectively conducted according to the heterogeneity statistics. Trial sequential analysis (TSA) was used to control random errors. RESULTS Ten studies involving 1107616 patients were involved in this meta-analysis. link3 No significant association was shown between aspirin users and non-aspirin users regarding the risk of aSAH [odds ratio (OR) 0.981, 95%confidential interval (CI) 0.773-1.312, P=0.897]. The results of subgroup analyses indicated that the risk of aSAH was notably associated with a short-term use of aspirin (3 years (OR 0.892, 95%CI 0.573-1.389, P=0.612), ≤2 times per week (OR 0.857, 95%CI 0.560-1.313, P=0.479), ≥3 times per week (OR 1.104, 95%CI 0.555-2.193, P=0.778) and former use (OR 1.029, 95%CI 0.482-2.196, P=0.941). CONCLUSIONS A short-term use of aspirin ( less then 3 months) is associated with an elevated risk of aSAH, while the role of its long-term use in either decreasing or increasing the risk of aSAH still requires well-designed, large-scale randomized control trials for verification. OBJECTIVES Management of incidental asymptomatic brain tumors in children is controversial due to lack of clear evidence-based guidelines. We present this systematic review in an attempt to highlight an optimal treatment paradigm. METHODS This systematic review was conducted in compliance with the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines. Databases were searched up to August 2019 using the keywords "incidental", "brain tumor" and "pediatric". Our main focus was on brain lesions suspected for neoplasm, diagnosed incidentally on neuroimaging in an otherwise asymptomatic patient less then 18 years old. Cystic, vascular, and inflammatory brain lesions were excluded. RESULTS Fourteen studies comprising 308 patients were included. All cases were diagnosed using MRI. The most common indications for imaging were headache (93; 30%) and trauma (72; 23%). Lesion distribution was supratentorial (179; 58%), infratentorial (121; 40%), and intraventricular (8; 3%). Out of 308 cases, 243 (79%) were managed with neuroradiological surveillance and 57 (19%) by upfront surgical excision. Of those managed conservatively, 177 (73%) remained stable within a mean follow-up of 30 months, 54 (22%) progressed, and 12 (5%) spontaneously regressed. Meanwhile, upfront excision achieved complete remission in all 57 cases over a mean follow-up of 68.3 months. CONCLUSION A small body of evidence has emerged, highlighting the marked heterogeneity and contradictory results between the available studies, limiting our ability to draw solid conclusions. At this point, the decision between surgery and "watchful waiting" should be tailored on an individual patient basis depending on suspicion of malignancy, clinical or radiologic progression, and parental preference.