Impact of neoadjuvant treatment on total mesorectal excision for ultra-low rectal cancers

<p>Abstract</p> <p>Background</p> <p>This study reviewed the impact of pre-operative chemoradiotherapy or post-operative chemotherapy and/or radiotherapy on total mesorectal excision (TME) for ultralow rectal cancers that required either low anterior resection with peranal coloanal anastomosis or abdomino-perineal resection (APR). We examined surgical complications, local recurrence and survival.</p> <p>Methods</p> <p>Of the 1270 patients who underwent radical resection for rectal cancer from 1994 till 2007, 180 with tumors within 4 cm with either peranal coloanal anastomosis or APR were analyzed. Patients were compared in groups that had surgery only (Group A), pre-operative chemoradiotherapy (Group B), and post-operative therapy (Group C).</p> <p>Results</p> <p>There were 115 males and the mean age was 65.43 years (range 30-89). APR was performed in 134 patients while 46 had a sphincter-preserving resection with peranal coloanal anastomosis. The mean follow-up period was 52.98 months (range: 0.57 to 178.9). There were 69, 58 and 53 patients in Groups A, B, and C, respectively. Nine patients in Group B could go on to have sphincter-saving rectal resection. The overall peri-operative complication rate was 43.4% in Group A vs. 29.3% in Group B vs. 39.6% in Group C, respectively. The local recurrence rate was significantly lower in Group B (8.6.9% vs. 21.7% in Group A vs. 33.9% in Group C) <it>p < 0.05</it>. The 5-year cancer-specific survival rates for Group A was 49.3%, Group B was 69.9% and Group C was 38.8% (<it>p </it>= 0.14).</p> <p>Conclusion</p> <p>Pre-operative chemoradiation in low rectal cancer is not associated with a higher incidence of peri-operative complications and its benefits may include reduction local recurrence.</p

Non invasive prenatal testing for single gene disorders:Exploring the ethics

Non-invasive prenatal testing for single gene disorders is now clearly on the horizon. This new technology offers obvious clinical benefits such as safe testing early in pregnancy. Before widespread implementation, it is important to consider the possible ethical implications. Four hypothetical scenarios are presented that highlight how ethical ideals of respect for autonomy, privacy and fairness may come into play when offering non-invasive prenatal testing for single gene disorders. The first scenario illustrates the moral case for using these tests for ‘information only', identifying a potential conflict between larger numbers of women seeking the benefits of the test and the wider social impact of funding tests that do not offer immediate clinical benefit. The second scenario shows how the simplicity and safety of non-invasive prenatal testing could lead to more autonomous decision-making and, conversely, how this could also lead to increased pressure on women to take up testing. In the third scenario we show how, unless strong safeguards are put in place, offering non-invasive prenatal testing could be subject to routinisation with informed consent undermined and that woman who are newly diagnosed as carriers may be particularly vulnerable. The final scenario introduces the possibility of a conflict of the moral rights of a woman and her partner through testing for single gene disorders. This analysis informs our understanding of the potential impacts of non-invasive prenatal testing for single gene disorders on clinical practice and has implications for future policy and guidelines for prenatal care

Reliable Detection of Paternal SNPs within Deletion Breakpoints for Non-Invasive Prenatal Exclusion of Homozygous α0-Thalassemia in Maternal Plasma

Reliable detection of large deletions from cell-free fetal DNA (cffDNA) in maternal plasma is challenging, especially when both parents have the same deletion owing to a lack of specific markers for fetal genotyping. In order to evaluate the efficacy of a non-invasive prenatal diagnosis (NIPD) test to exclude α-thalassemia major that uses SNPs linked to the normal paternal α-globin allele, we established a novel protocol to reliably detect paternal SNPs within the (−−SEA) breakpoints and performed evaluation of the diagnostic potential of the protocol in a total of 67 pregnancies, in whom plasma samples were collected prior to invasive obstetrics procedures in southern China. A group of nine SNPs identified within the deletion breakpoints were scanned to select the informative SNPs in each of the 67 couples DNA by multiplex PCR based mini-sequencing technique. The paternally inherited SNP allele from cffDNA was detected by allele specific real-time PCR. A protocol for reliable detection of paternal SNPs within the (−−SEA) breakpoints was established and evaluation of the diagnostic potential of the protocol was performed in a total of 67 pregnancies. In 97% of the couples one or more different SNPs within the deletion breakpoint occurred between paternal and maternal alleles. Homozygosity for the (−−SEA) deletion was accurately excluded in 33 out of 67 (49.3%, 95% CI, 25.4–78.6%) pregnancies through the implementation of the protocol. Protocol was completely concordant with the traditional reference methods, except for two cases that exhibited uncertain results due to sample hemolysis. This method could be used as a routine NIPD test to exclude gross fetal deletions in α-thalassemia major, and could further be employed to test for other diseases due to gene deletion

Down-Regulated NOD2 by Immunosuppressants in Peripheral Blood Cells in Patients with SLE Reduces the Muramyl Dipeptide-Induced IL-10 Production

Pattern recognition receptors (PRRs) such as Toll-like receptors are aberrantly expressed of peripheral blood mononuclear cells (PBMCs) in systemic lupus erythematosus (SLE) patients, for playing immunopathological roles. basal productions of cytokines (IL-6, IL-8 and IL-10) were significantly increased in immunosuppressant naïve patients and patients with active disease despite immunosuppressants compared with HCs. Upon MDP stimulaiton, relative induction (%) of cytokines (IL-1β) from PBMC was significantly increased in immunosuppressant naïve patients with inactive disease, and patients with active disease despite immunosuppressant treatment compared with HCs. Immunosuppressant usage was associated with a decreased basal production and MDP induced relative induction (%) of IL-10 in patients with inactive disease compared with immunosuppressant naïve patients and HCs.Bacterial exposure may increase the NOD2 expression in monocytes in immunosuppressant naïve SLE patients which can subsequently lead to aberrant activation of PBMCs to produce proinflammatory cytokines, implicating the innate immune response for extracellular pathogens in the immunopathological mechanisms in SLE. Immunosuppressant therapy may downregulate NOD2 expression in CD8+ T lymphocytes, monocytes, and DCs in SLE patients which subsequently IL-10 reduction, contributing towards the regulation of immunopathological mechanisms of SLE, at the expense of increasing risk of bacterial infection

Advancing brain barriers RNA sequencing: guidelines from experimental design to publication

Background: RNA sequencing (RNA-Seq) in its varied forms has become an indispensable tool for analyzing differential gene expression and thus characterization of specific tissues. Aiming to understand the brain barriers genetic signature, RNA seq has also been introduced in brain barriers research. This has led to availability of both, bulk and single-cell RNA-Seq datasets over the last few years. If appropriately performed, the RNA-Seq studies provide powerful datasets that allow for significant deepening of knowledge on the molecular mechanisms that establish the brain barriers. However, RNA-Seq studies comprise complex workflows that require to consider many options and variables before, during and after the proper sequencing process.Main body: In the current manuscript, we build on the interdisciplinary experience of the European PhD Training Network BtRAIN (https://www.btrain-2020.eu/) where bioinformaticians and brain barriers researchers collaborated to analyze and establish RNA-Seq datasets on vertebrate brain barriers. The obstacles BtRAIN has identified in this process have been integrated into the present manuscript. It provides guidelines along the entire workflow of brain barriers RNA-Seq studies starting from the overall experimental design to interpretation of results. Focusing on the vertebrate endothelial blood–brain barrier (BBB) and epithelial blood-cerebrospinal-fluid barrier (BCSFB) of the choroid plexus, we provide a step-by-step description of the workflow, highlighting the decisions to be made at each step of the workflow and explaining the strengths and weaknesses of individual choices made. Finally, we propose recommendations for accurate data interpretation and on the information to be included into a publication to ensure appropriate accessibility of the data and reproducibility of the observations by the scientific community.Conclusion: Next generation transcriptomic profiling of the brain barriers provides a novel resource for understanding the development, function and pathology of these barrier cells, which is essential for understanding CNS homeostasis and disease. Continuous advancement and sophistication of RNA-Seq will require interdisciplinary approaches between brain barrier researchers and bioinformaticians as successfully performed in BtRAIN. The present guidelines are built on the BtRAIN interdisciplinary experience and aim to facilitate collaboration of brain barriers researchers with bioinformaticians to advance RNA-Seq study design in the brain barriers community

Seasonal and spatial root biomass and water use efficiency of four forage legumes in semiarid northwest China

A field study was conducted to determine seasonal root biomass, root spatial distribution and water use efficiency (WUE) in milkvetch (Astragalus adsurgens Pall.), sainfoin (Onobrychis viciaefolia Scop.), alfalfa (Medicago sativa L.) and Lespedeza davurica (L. davurica) grown in semiarid region on the Loess Plateau, northwestern China. Soil core method ((emptyset)9 cm) was used to determine root biomass in April, September and November in 2005. For each species, root biomass vertical distribution was measured down to 150 cm in increments of 0-20, 20-40, 40-60, 60-90, 90-120 and 120-150 cm for inter-rows, between plants and at the center of plants respectively. Roots were distributed throughout the profile with a high concentration at the top and decreasing with soil depth. Root biomass was mainly concentrated in 0-60 cm strata between rows and between plants of each species while at the center of plants it mainly distributed in 0-20 cm strata. Except L. davurica whose root biomass reached the maximum in September, root biomass of the other three legumes reached the maximum in November. Shoot biomass continued to increase from April to November for all the four legumes. In November, the root biomass for milkvetch and alfalfa accounted for about 2.93 and 2.30% of the total biomass (root plus shoot) respectively, while in sainfoin and L. davurica it accounted for 6.00 and 4.44% respectively. There were significant differences between the four legumes in WUE, and the order was same as shoot biomass, ranked as milkvetch&gt;alfalfa&gt;sainfoin&gt;L. davurica. The seasonal and yearly high shoot biomass and low proportion of root biomass resulting to low root : shoot ratio may explain the significantly higher WUE of milkvetch and alfalfa in comparison to sainfoin and L. davurica

Evaluation of switchgrass and sainfoin intercropping under 2:1 row-replacement in semiarid region, northwest China

Field experiments were carried out under natural conditions to compare the aboveground biomass, root growth and distribution, and topsoil nutrition contents of switchgrass (Panicum virgatum) and sainfoin (Onobrychis viciaefolia) grown in sole cropping and 2: 1 row-replacement intercropping in semiarid loess region on Loess Plateau of northwest China. The sole and intercropping was compared based on the aboveground biomass, water use efficiency (WUE), soil organic matter (SOM) and total nitrogen (TN), and root biomass and distribution. The aboveground biomass production was measured every year at the end of growth seasons in 2001-2005. Root biomass and vertical distribution were studied only in 2005. Topsoil SOM and TN contents were measured discontinuously during the study period. Results showed that intercropping reduced the aboveground biomass production of sainfoin significantly compared with its pure stand. The WUE of sole switchgrass was significantly the highest in each year among the three stands, while the intercropped stand was significantly higher than sole sainfoin on five-year averaged. The aggressivity of sainfoin to swichgrass decreased along with the growth years. Before 2005, the land equivalent ratio (LER) was bigger than 1.0 and actual yield loss (AYL) was positive. Under intercropping, root biomass input and root: shoot ratio in switchgrass reduced, while sainfoin inputs more photosynthate to root growth. Switchgrass had high root biomass and wide distribution vertically and horizontally indicates a higher belowground competitive ability in the mixture. It indicated a flexible distribution strategy of switchgrass tending to increase soil exploitation and space sequestration efficiency in soil layers. SOM and TN increased significantly for the three stands at the end of the fourth growth year, especially for the mixture. Switchgrass and sainfoin intercropped under 2: 1 row-replacement can be a short-term rotation tillage choice with respect to soil management in the area