Non-kutanöz Periferik T-hücreli Lenfomalarda Klinik Özellikler ve Tedavi Sonuçlarına ilişkin Gerçek Yaşam Deneyimi:Türk Hematoloji Araştırma ve Eğitim Grubunun Çok Merkezli Çalışması

Objective: Peripheral T-cell lymphomas (PTCLs) are an uncommon and quite heterogeneous group of disorders, representing only 10%-15% of all non-Hodgkin lymphomas. Although both molecular and clinical studies have increased in recent years, we still have little knowledge regarding real-life practice with PTCLs. In this study, we aimed to investigate the clinical characteristics and treatment outcomes of a large population-based cohort of patients presenting with systemic non-cutaneous PTCL. Materials and Methods: We conducted a multicenter retrospective analysis of 190 patients consecutively diagnosed and treated with non-cutaneous PTCLs between 2008 and 2016. Results: Considering all first-line treatment combinations, the overall response rate was 65.9% with 49.4% complete remission (n=81) and 16.5% partial response (n=27). The 5-year overall survival and event-free survival rates were significantly different between the transplant and non-transplant groups (p<0.01, and p=0.033, respectively). Conclusion: The retrospective analysis of a large volume of real-life data on the Turkish experience regarding non-cutaneous PTCL patients showed consistent results compared to other unselected PTCL cohorts with some minor differences in terms of survival and transplantation outcomes. The long-term outcome of patients who receive autologous hematopoietic cell transplantation as part of upfront consolidation or salvage therapy is favorable compared to patients who are unable to receive high-dose therapy. © 2022 by Turkish Society of Hematology Turkish Journal of Hematology, Published by Galenos Publishing House

Adventures in the Enormous: A 1.8 Million Clone BAC Library for the 21.7 Gb Genome of Loblolly Pine

Loblolly pine (LP; Pinus taeda L.) is the most economically important tree in the U.S. and a cornerstone species in southeastern forests. However, genomics research on LP and other conifers has lagged behind studies on flowering plants due, in part, to the large size of conifer genomes. As a means to accelerate conifer genome research, we constructed a BAC library for the LP genotype 7-56. The LP BAC library consists of 1,824,768 individually-archived clones making it the largest single BAC library constructed to date, has a mean insert size of 96 kb, and affords 7.6X coverage of the 21.7 Gb LP genome. To demonstrate the efficacy of the library in gene isolation, we screened macroarrays with overgos designed from a pine EST anchored on LP chromosome 10. A positive BAC was sequenced and found to contain the expected full-length target gene, several gene-like regions, and both known and novel repeats. Macroarray analysis using the retrotransposon IFG-7 (the most abundant repeat in the sequenced BAC) as a probe indicates that IFG-7 is found in roughly 210,557 copies and constitutes about 5.8% or 1.26 Gb of LP nuclear DNA; this DNA quantity is eight times the Arabidopsis genome. In addition to its use in genome characterization and gene isolation as demonstrated herein, the BAC library should hasten whole genome sequencing of LP via next-generation sequencing strategies/technologies and facilitate improvement of trees through molecular breeding and genetic engineering. The library and associated products are distributed by the Clemson University Genomics Institute (www.genome.clemson.edu)

Effects of estrogens and bladder inflammation on mitogen-activated protein kinases in lumbosacral dorsal root ganglia from adult female rats

BACKGROUND: Interstitial cystitis is a chronic condition associated with bladder inflammation and, like a number of other chronic pain states, symptoms associated with interstitial cystitis are more common in females and fluctuate during the menstrual cycle. The aim of this study was to determine if estrogens could directly modulate signalling pathways within bladder sensory neurons, such as extracellular signal-related kinase (ERK) and p38 mitogen-activated protein (MAP) kinases. These signalling pathways have been implicated in neuronal plasticity underlying development of inflammatory somatic pain but have not been as extensively investigated in visceral nociceptors. We have focused on lumbosacral dorsal root ganglion (DRG) neurons projecting to pelvic viscera (L1, L2, L6, S1) of adult female Sprague-Dawley rats and performed both in vitro and in vivo manipulations to compare the effects of short- and long-term changes in estrogen levels on MAPK expression and activation. We have also investigated if prolonged estrogen deprivation influences the effects of lower urinary tract inflammation on MAPK signalling. RESULTS: In studies of isolated DRG neurons in short-term (overnight) culture, we found that estradiol and estrogen receptor (ER) agonists rapidly stimulated ER-dependent p38 phosphorylation relative to total p38. Examination of DRGs following chronic estrogen deprivation in vivo (ovariectomy) showed a parallel increase in total and phosphorylated p38 (relative to beta-tubulin). We also observed an increase in ERK1 phosphorylation (relative to total ERK1), but no change in ERK1 expression (relative to beta-tubulin). We observed no change in ERK2 expression or phosphorylation. Although ovariectomy increased the level of phosphorylated ERK1 (vs. total ERK1), cyclophosphamide-induced lower urinary tract inflammation did not cause a net increase of either ERK1 or ERK2, or their phosphorylation. Inflammation did, however, cause an increase in p38 protein levels, relative to beta-tubulin. Prior ovariectomy did not alter the response to inflammation. CONCLUSIONS: These results provide new insights into the complex effects of estrogens on bladder nociceptor signalling. The diversity of estrogen actions in these ganglia raises the possibility of developing new ways to modulate their function in pelvic hyperactivity or pain states

COVID-19 infection in adult patients with hematological malignancies: a European Hematology Association Survey (EPICOVIDEHA)

Background: Patients with hematological malignancies (HM) are at high risk of mortality from SARS-CoV-2 disease 2019 (COVID-19). A better understanding of risk factors for adverse outcomes may improve clinical management in these patients. We therefore studied baseline characteristics of HM patients developing COVID-19 and analyzed predictors of mortality. Methods: The survey was supported by the Scientific Working Group Infection in Hematology of the European Hematology Association (EHA). Eligible for the analysis were adult patients with HM and laboratory-confirmed COVID-19 observed between March and December 2020. Results: The study sample includes 3801 cases, represented by lymphoproliferative (mainly non-Hodgkin lymphoma n = 1084, myeloma n = 684 and chronic lymphoid leukemia n = 474) and myeloproliferative malignancies (mainly acute myeloid leukemia n = 497 and myelodysplastic syndromes n = 279). Severe/critical COVID-19 was observed in 63.8% of patients (n = 2425). Overall, 2778 (73.1%) of the patients were hospitalized, 689 (18.1%) of whom were admitted to intensive care units (ICUs). Overall, 1185 patients (31.2%) died. The primary cause of death was COVID-19 in 688 patients (58.1%), HM in 173 patients (14.6%), and a combination of both COVID-19 and progressing HM in 155 patients (13.1%). Highest mortality was observed in acute myeloid leukemia (199/497, 40%) and myelodysplastic syndromes (118/279, 42.3%). The mortality rate significantly decreased between the first COVID-19 wave (March–May 2020) and the second wave (October–December 2020) (581/1427, 40.7% vs. 439/1773, 24.8%, p value < 0.0001). In the multivariable analysis, age, active malignancy, chronic cardiac disease, liver disease, renal impairment, smoking history, and ICU stay correlated with mortality. Acute myeloid leukemia was a higher mortality risk than lymphoproliferative diseases. Conclusions: This survey confirms that COVID-19 patients with HM are at high risk of lethal complications. However, improved COVID-19 prevention has reduced mortality despite an increase in the number of reported cases.EPICOVIDEHA has received funds from Optics COMMITTM (COVID-19 Unmet Medical Needs and Associated Research Extension) COVID-19 RFP program by GILEAD Science, United States (Project 2020-8223)

Melatonin ameliorates oxidative damage in hyperglycemia-induced liver injury

Purpose: Melatonin (N-acetyl-5-methoxy-tryptamine) is synthesized mainly by the pineal gland and its antioxidant properties have been demonstrated both in short and long term studies. Our aim was to clarify the effects of hyperglycemia and to administer melatonin on lipid peroxidation, protein oxidation and oxidative DNA damage in rat. Methods: Malondialdehyde (MDA), protein carbonyl (PCO) and total thiol (T-SH) levels were determined in plasma and liver tissue, glutathione (GSH) levels in erythrocyte and liver tissue, and 8-hydroxy-2-deoxyguanosine (8-OHdG) levels in plasma and liver. Thirty-eight male Wistar rats were divided into four groups: 1 - injected with saline (n = 8), 2 - injected with melatonin (n = 10), 3 - injected with STZ (65 mg/kg, i.p.) (diabetic group) (n = 10) and 4 - injected with melatonin (10 mg/kg/day, i.p.) and STZ (65 mg/kg, i.p.) (n = 10) for 8 weeks (diabetic+ melatonin group). Colorimetric methods were used to determine the level of the oxidative stress markers. 8-OhdGwas measured using ELISA. Results: MDA, PCO and 8-OHdG levels in the plasma and the liver homogenates of diabetic rats were higher than controls and were significantly reduced after melatonin treatment. T-SH and GSH levels in samples were markedly reduced in untreated diabetic rats compared with control rats; however, these parameters were increased in diabetic rats following melatonin treatment. Conclusion: Our findings showed that melatonin administration partially ameliorated oxidative damage in liver injury in STZ-induced diabetic rats. The present study suggests that melatonin functions as a potent antioxidant agent in diabetes. Melatonin, a nutritional supplement, may be a good therapeutic option for diabetic patients

A reliable pancreaticojejunal anastomosis with V-Loc 180 wound closure device for soft pancreatic stump

WOS: 000335085400046PubMed ID: 24901167Background/Aims: Although mortality rates decreased in recent years, pancreaticoduodenectomy is still associated with high morbidity rates. Pancreatic fistula is the leading cause of morbidity after pancreaticojejunal anastomosis and commonly occurs in soft pancreas. The objective of this study is to compare outcomes of conventional modified invaginated end to side pancreaticojejunostomy with a new practical method using V-Loc (TM) 180 wound closure device in soft pancreas. Methodology: Between December 2011 and August 2013, a total of 90 pancreaticoduodenectomy procedures were performed in our hospital. 28 of them were defined as soft pancreas according to attending surgeon and included in this study. Patients were divided into two groups consecutively and analysed for postoperative pancreatic fistula (POPF) rate, length of stay, operation time, cost and particular duration of anastomosis. Pancreatic fistulas were classified according to International Study Group on Pancreatic Fistula (ISGPF) definition. Results: 1 grade A and 2 grade B fistulas appeared in V-Loc group (Group 1), whereas 1 grade A, 2 grade B and 1 grade C fistulas appeared in conventional anastomosis group (Group 2). Conclusions: Pancreaticojejunostomy with V-Loc suture is a convenient method in soft pancreas and can be performed safely

Effects of dietary propolis and vitamin E on growth performance and antioxidant status in blood of juvenile Rainbow trout, Oncorhynchus mykiss (Teleostei: Salmoniformes) under different flow rates

The present study investigated the effects of propolis and vitamin E supplementation in diets of juvenil rainbow trout subjected to two different flow rates with or without flow stress (0.9 and 2.1 l/min, respectively) on final weigth (FW), condition factor (CF), feed conservation ratio (FCR), protein efficiency ratio (PER) and vitamin A, C and E concentrations and malondialdehyde (MDA) levels in serum as well as plasma superoxide dismutase (SOD) activity. The experimental groups were as follows: group C was fed a basal diet, group P10 was fed a basal diet supplemented with 10 g propolis/kg, group P30 was fed a basal diet supplemented with 30 g propolis/kg, group E60 was fed a basal diet supplemented with 60 mg vitamin E/kg. CF and PER were not different among all diets groups for both flow rate treatments (p > 0.05). The FCR improved in P10, P30 and E60 diet groups compared to C diet group at 2.1 l/min flow rate (p < 0.05). The FCR of E60 and P30 were found to be better than C and P10 diet groups at 0.9 l/min flow rate (p < 0.05). Vitamin E and propolis supplementations did not affect vitamin A concentration of serum for either flow rate (p > 0.05). Fish fed with diet E60had higher serum vitamin E concentration than other groups (p < 0.05). Serum Vitamin C concentration was only affected by the propolis supplemented diets. MDA level of E60 group was found significantly lower comperad to other groups for both flow rate (p < 0.05). Plasma SOD activity significantly decreased in the E60 group compared to other groups at 2.1 l/min flow rate (p < 0.05). But plasma SOD activity was not different among all diets groups at 0.9 l/min flow rate (p > 0.05)