50 research outputs found
Oncological outcome after local treatment for early stage rectal cancer
No full text(c) The Author/sBACKGROUND: Treatment of early rectal cancer is evolving towards organ-preserving therapy which includes endoscopic resection and transanal approaches. We aimed to explore the role of local treatments such as endoscopic polypectomy (Endoscopic Mucosal Resection (EMR) or Endoscopic submucosal dissection (ESD)) and transanal endoscopic microsurgery/ transanal minimal invasive surgery (TEM/TAMIS) in patients who had early rectal cancer. We considered these outcomes alongside conventional major surgery using total mesorectal excision (TME) for early stage disease.
METHODS: All patients identified at MDT with early stage rectal cancer at our institution between 2010 and 2019 were included. Long-term outcomes in terms of local recurrence, survival and procedure-specific morbidity were analysed.
RESULTS: In total, 536 patients with rectal cancer were identified, of which 112 were included based on their pre-operative identification at the MDT on the basis that they had node-negative early rectal cancer. Among these, 30 patients (27%) had the lesion excised by flexible endoscopic polypectomy techniques (EMR/ESD), 67 (60%) underwent TEM/TAMIS and 15 (13%) had major surgery. There were no differences in patient demographics between the three groups except for TEM/TAMIS patients being more likely to be referred from another hospital (p < 0.001) and they were less active (WHO performance status p = 0.04). There were no significant differences in overall survival rates and cancer-specific survival between the three treatment groups. The 5-year overall survival rate for endoscopic polypectomy, TEM/TAMIS or major resection was 96% versus 90% and 88%, respectively (p = 0.89). The 5- year cancer-specific survival rate was 96%, versus 96% and 100%, respectively (p = 0.74).
CONCLUSION: Endoscopic polypectomy by EMR/ESD is an appropriate local treatment for early stage rectal cancer in selected patients. It is possible to achieve good oncological outcomes with a polypectomy similar to TEM/TAMIS and major surgery; however, a multidisciplinary approach is necessary enabling close surveillance and the use of adjuvant radiotherapy.Publish
From field to rumen: foliar fungicide application on corn and its effects on the corn plant, corn silage, and Holstein cow performance
No full textAn increasing global population, decreasing amount of arable land available for crop production in the United States, and an increased global demand for protein in the human diet encourage crop and livestock producers to seek solutions to improve the efficiency of producing large crop yields. The interaction of fungi and corn plants in the field threaten yields, decreasing the efficiency of food production and the nutritive quality of feedstuffs for ruminants. Fungicides can assist corn plants in protection from fungal infection by limiting yield losses and increasing the nutritive quality of the plant material. However, little is known about how various applications of fungicide on corn change the nutrients of individual parts of the corn plant, alter the fermentation of corn silage once ensiled, and affect the milk production when fed to dairy cattle. Therefore, the objectives of the present study were to investigate various applications of fungicide on: corn associated with the nutritive profile and growth of corn leaves, ears, stalks, and flag leaves; once ensiled, on the nutritive and fermentative profile of corn silage; and when corn silage is fed to dairy cattle on milk production, milk components, blood metabolites, and cow health. Corn from two growing seasons, 2014 and 2015, with different fungicide treatments was included in this study. Corn grown during the summer of 2014 was ensiled and fed to dairy cows, while corn grown during the summer of 2015 evaluated the plant and corn silage.
In 2014, treatments were as follows: corn silage with no application of foliar fungicide (CON); corn silage received one application of pyraclostrobin and fluxapyroxad (PYR+FLUX) foliar fungicide (Priaxor®; BASF Corp.) at corn stage V5 (V5); corn silage received one application of PYR+FLUX at corn stage V5 plus another application of PYR+FLUX at corn stage V8 (V5/V8); corn silage received one application of PYR+FLUX at corn stage V5, one application of PYR+FLUX at corn stage V8, plus a third application of pyraclostrobin and metconazole (PYR+MET) foliar fungicide (Headline AMP®; BASF Corp) at corn stage R1 (V5/V8/R1). Corn was harvested at 31.2% DM and ensiled for more than 200 d before feeding. Treatments were fed to cows for 5 wk with only the last week being used for statistical inferences. Three contrast statements were used: contrast 1: CON vs. TRT compared control to the average of treatments fed corn silage sprayed with foliar fungicide (V5, V5/V8, and V5/V8/R1); contrast 2: V5 vs. V5/V8 compared the treatment fed corn silage sprayed at V5 to the treatment fed corn silage sprayed at V5 and V8; and contrast 3: V5/V8 vs. V5/V8/R1 compares the treatment fed corn silage sprayed at V5 and V8 to the treatment fed corn silage sprayed at V5, V8, and R1. No differences in DMI (19.5, 19.5, 20.8, and 20.4 kg for CON, V5, V5/V8, and V5/V8/R1, respectively) or milk yield (30.5, 31.2, 29.1, and 29.3 kg/d) were observed. However, cows in V5 when compared with cows in V5/V8 tended, to produce more 3.5% fat corrected milk (FCM; 32.42 and 28.58 kg/d, respectively) and energy corrected milk (ECM; 31.35 and 27.76 kg/d, respectively). Concentration of milk lactose tended to be greater for cows fed corn silage treated with foliar fungicide when compared with CON.
In 2015, the study was split into two parts, but the fungicide treatment was the same for both part one and part two. Treatments were as follows: control (CON), corn receiving no foliar fungicide application; treatment 1 (V5), where corn received a mixture of pyraclotrobin and fluxapyroxad foliar fungicide (Priaxor, BASF Corp.) corn vegetative stage 5 (V5); treatment 2 (V5+R1), where corn received two applications of foliar fungicide, a mixture of pyraclotrobin and fluxapyroxad at V5 and a mixture of pyraclostrobin + metconazole foliar fungicide (Headline AMP; BASF Corp.) at corn reproductive stage 1 (R1), and treatment 3 (R1), in which corn received one applications of pyraclostrobin + metconazole foliar fungicide at R1. Evaluators at R1 and R3 reported signs of Gray Leaf Spot and Northern Leaf Blight on the foliage. In part one, 24 individual corn plants from each treatment were collected R1 and R3 for weight and length measurement. At each collection, treatment corn plants were disassembled into leaves, stalks, flag leaf, and ears for nutrient analysis. The effect of foliar fungicide treatment, corn growth stage, and treatment by growth stage was evaluated on a dry matter basis. Interactions of fungicide applications on corn by collection time point were observed for the number of yellow leaves (0, 0, 0, and 0 at R1 and 0.85, 0.77, 0.42, and 0.44 for CON, V5, V5+R1, and R1 at R3 respectively; P = 0.03) and the height of the stalk (2.89, 2.94, 2.92, and 2.96 m at R1, and 2.50, 2.91, 3.05, and 2.80 for CON, V5, V5+R1, and R1 at R3; P = 0.02), with greater values for corn treated with fungicide than untreated. Corn stalks from corn treated with fungicide had greater concentrations of lignin compared with untreated (46, 56, 64, and 50 g/kg DM for CON, V5, V5+R1, and R1, respectively), with the greatest value from corn in V5+R1. Corn leaves from corn treated with fungicide had lower concentrations of ADF (333, 331, 283, and 330 g/kg DM for CON, V5, V5+R1, and R1, respectively) and NDF (569, 584, 524, and 554 g/kg DM for CON, V5, V5+R1, and R1, respectively) compared with untreated, with the lowest concentrations of ADF and NDF from corn in V5+R1. Interactions of applications of fungicide on corn by collection time point in corn leaves were observed for ADF (329, 335, 338, and 336 g/kg at R1, and 337, 326, 228, and 304 g/kg at R3 for CON, V5, V5+R1, and R1, respectively; P = 0.008), Na (14, 12, 10, and 7 g/kg at R1, and 6, 5, 7, and 5 g/kg at R3 for CON, V5, V5+R1, and R1, respectively; P = 0.02), and Cu (12, 12, 11, and 13 PPM at R1, and 15, 15, 18, and 17 PPM at R3 for CON, V5, V5+R1, and R1, respectively; P = 0.03).
In part two, the effect of treatment, ensiling time, and treatment by ensiling time was evaluated on a laboratory scale. Samples of the chopped corn were collected at harvest, prepared as 0.9-kg silos, and vacuumed sealed (28 × 36 cm). Chopped corn ensiled for 0 d was frozen on the day of harvest, while silos for 30, 90, and 150 d were left in the vacuum-sealed bags for each respective time frame and frozen for later analysis. Applications of foliar fungicide on corn ensiled as corn silage decreased dry matter (335, 319, 315, and 317 g/kg DM for CON, V5, V5+R1, and R1, respectively), but increased crude protein (81, 85, 82, and 87 g/kg DM for CON, V5, V5+R1, and R1, respectively), water soluble carbohydrates (38, 40, 46, and 52 g/kg DM for CON, V5, V5+R1, and R1, respectively), and lactic acid (46.5, 50.1, 50.9, and 55.0 g/kg for CON, V5, V5+R1, and R1, respectively). Applications of fungicide at R1 had the lowest lignin compared to treatments (20 g/kg DM for R1 vs 24, 24, 26 g/kg DM for CON, V5, and V5+R1, respectively), and corn silage in V5 had greater milk kg/MT DM (1631 kg/ton DM for V5 vs. 1511, 1585, and 1576 kg/MT DM for CON, V5+R1, and R1, respectively; P = 0.04). Length of ensiling postharvest affected the dry matter (327, 314, 325, and 320 g/kg for 0, 30, 90, and 150 d, respectively; P = 0.03), crude protein (81, 85, 84, and 86 g/kg for 0, 30, 90, and 150 d; P < 0.0001), and pH (5.74, 3.75, 3.80, and 3.80 for 0, 30, 90, and 150 d; P < 0.0001) of corn silage. Significant interactions between foliar fungicide applications on corn ensiled as corn silage and length of ensiling postharvest were observed for water soluble carbohydrates (80, 91, 111, and 125 g/kg at 0 d; 16, 17, 19, 22 g/kg at 30 d; 25, 25, 26, and 32 g/kg at 90 d; 31, 28, 27 and 32 g/kg at 150 d for CON, V5+R1, and R1, respectively; P = 0.03), and lactic acid (1.0, 0.5, 0.4, and 0.5 g/kg at 0 d; 54.3, 67.8, 64.4, 71.9 g/kg at 30 d; 63.4, 68.5, 69.2, and 71.1 g/kg at 90 d; and 62.7, 63.7, 69.7, and 76.6 g/kg at 150 d for CON, V5+R1, and R1, respectively; P = 0.03).
In conclusion, fungicide application on corn affected the nutritional profile differently depending on the part of the plant. Once ensiled, fungicide application on corn impacted the nutritional composition and fermentation of corn silage ensiled for varying lengths of time postharvest. Finally, corn silage from corn receiving foliar fungicide fed to cows impacted milk production and composition. Cows fed corn silage receiving foliar fungicide treatment at V5 had greater FCM and ECM than cows fed corn silage receiving foliar fungicide treatment at V5 and V8. Results from 2015 corn indicate applications of fungicide on corn reduced the number of yellow leaves and increased the height of the corn stalk. Applications of fungicide on corn atV5 and R1 resulted in the greatest concentration of lignin in the stalk, but applications of fungicide on corn at both V5 and R1 reduced the concentration of ADF and NDF in the corn leaves. Applications of fungicide on corn ensiled as corn silage reduced the DM content, and applications of fungicide at R1 resulted in the lowest concentration of lignin in corn silage. Foliar fungicide treated corn and, then corn silage, increased the nutritive quality of the plant material and corn silage by decreasing the fibrous content, and resulted in increased FCM and ECM when fed to dairy cows.Submission published under a 24 month embargo labeled 'U of I Access', the embargo will last until 2018-08-01The student, Caroline Kalebich, accepted the attached license on 2016-07-05 at 16:44.The student, Caroline Kalebich, submitted this Thesis for approval on 2016-07-05 at 16:51.This Thesis was approved for publication on 2016-07-06 at 11:11.DSpace SAF Submission Ingestion Package generated from Vireo submission #9763 on 2016-11-10 at 12:24:53Made available in DSpace on 2016-11-10T18:39:17Z (GMT). No. of bitstreams: 2
KALEBICH-THESIS-2016.pdf: 1546705 bytes, checksum: 5d5d7e7c154e4466f36d31e019aaf54a (MD5)
LICENSE.txt: 4214 bytes, checksum: 9871ef810bafcf1d42efa73ba8c41b33 (MD5)
Previous issue date: 2016-07-06Embargo set by: Seth Robbins for item 95453
Lift date: 2018-11-10T18:39:22Z
Reason: Author requested U of Illinois access only (OA after 2yrs) in Vireo ETD systemEmbargo set by: Seth Robbins for item 95453
Lift date: 2018-11-10T18:43:22Z
Reason: Author requested U of Illinois access only (OA after 2yrs) in Vireo ETD systemU of I Only Restriction Lifted for Item 95453 on 2018-11-11T10:15:45Z
Identification of heart rate-associated loci and their effects on cardiac conduction and rhythm disorders
No full textElevated resting heart rate is associated with greater risk of cardiovascular disease and mortality. In a 2-stage meta-analysis of genome-wide association studies in up to 181,171 individuals, we identified 14 new loci associated with heart rate and confirmed associations with all 7 previously established loci. Experimental downregulation of gene expression in Drosophila melanogaster and Danio rerio identified 20 genes at 11 loci that are relevant for heart rate regulation and highlight a role for genes involved in signal transmission, embryonic cardiac development and the pathophysiology of dilated cardiomyopathy, congenital heart failure and/or sudden cardiac death. In addition, genetic susceptibility to increased heart rate is associated with altered cardiac conduction and reduced risk of sick sinus syndrome, and both heart rate-increasing and heart rate-decreasing variants associate with risk of atrial fibrillation. Our findings provide fresh insights into the mechanisms regulating heart rate and identify new therapeutic targets
Genome-wide meta-analysis identifies 11 new loci for anthropometric traits and provides insights into genetic architecture
No full textApproaches exploiting trait distribution extremes may be used to identify loci associated with common traits, but it is unknown whether these loci are generalizable to the broader population. In a genome-wide search for loci associated with the upper versus the lower 5th percentiles of body mass index, height and waist-to-hip ratio, as well as clinical classes of obesity, including up to 263,407 individuals of European ancestry, we identified 4 new loci (IGFBP4, H6PD, RSRC1 and PPP2R2A) influencing height detected in the distribution tails and 7 new loci (HNF4G, RPTOR, GNAT2, MRPS33P4, ADCY9, HS6ST3 and ZZZ3) for clinical classes of obesity. Further, we find a large overlap in genetic structure and the distribution of variants between traits based on extremes and the general population and little etiological heterogeneity between obesity subgroups
Management strategy after diagnosis of Abernethy malformation: a case report
No full textAbstract Introduction The Abernethy malformation is a rare anomaly with a widely variable clinical presentation. Many diagnostic dilemmas have been reported. Nowadays, with the evolution of medical imaging, diagnosis can be made more easily, but management of patients with an Abernethy malformation is still open for discussion. Case presentation In this case study, we describe a 34-year-old Caucasian man who presented with a large hepatocellular carcinoma in the presence of an Abernethy malformation, which was complicated by the development of pulmonary arterial hypertension. Conclusion This case underlines the importance of regular examination of patients with an Abernethy malformation, even in older patients, to prevent complications and to detect liver lesions at an early stage.</p
Genetic association study of QT interval highlights role for calcium signaling pathways in myocardial repolarization.
No full textThe QT interval, an electrocardiographic measure reflecting myocardial repolarization, is a heritable trait. QT prolongation is a risk factor for ventricular arrhythmias and sudden cardiac death (SCD) and could indicate the presence of the potentially lethal mendelian long-QT syndrome (LQTS). Using a genome-wide association and replication study in up to 100,000 individuals, we identified 35 common variant loci associated with QT interval that collectively explain ∼8-10% of QT-interval variation and highlight the importance of calcium regulation in myocardial repolarization. Rare variant analysis of 6 new QT interval-associated loci in 298 unrelated probands with LQTS identified coding variants not found in controls but of uncertain causality and therefore requiring validation. Several newly identified loci encode proteins that physically interact with other recognized repolarization proteins. Our integration of common variant association, expression and orthogonal protein-protein interaction screens provides new insights into cardiac electrophysiology and identifies new candidate genes for ventricular arrhythmias, LQTS and SCD
Conditional immortalization of human B cells by CD40 ligation
No full textIt is generally assumed that human differentiated cells have a limited life-span and proliferation capacity in vivo, and that genetic modifications are a prerequisite for their immortalization in vitro. Here we readdress this issue, studying the long-term proliferation potential of human B cells. It was shown earlier that human B cells from peripheral blood of healthy donors can be efficiently induced to proliferate for up to ten weeks in vitro by stimulating their receptor CD40 in the presence of interleukin-4. When we applied the same stimuli under conditions of modified cell number and culture size, we were surprised to find that our treatment induced B cells to proliferate throughout an observation period of presently up to 1650 days, representing more than 370 population doublings, which suggested that these B cells were immortalized in vitro. Long-term CD40-stimulated B cell cultures could be established from most healthy adult human donors. These B cells had a constant phenotype, were free from Epstein-Barr virus, and remained dependent on CD40 ligation. They had constitutive telomerase activity and stabilized telomere length. Moreover, they were susceptible to activation by Toll-like receptor 9 ligands, and could be used to expand antigen-specific cytotoxic T cells in vitro. Our results indicate that human somatic cells can evade senescence and be conditionally immortalized by external stimulation only, without a requirement for genetic manipulation or oncoviral infection. Conditionally immortalized human B cells are a new tool for immunotherapy and studies of B cell oncogenesis, activation, and function
Preparing for national school-based deworming in Kenya: the validation and large-scale distribution of school questionnaires with urinary schistosomiasis.
No full textOBJECTIVE: School questionnaires of self-reported schistosomiasis provide a rapid and simple approach for identifying schools at high risk of Schistosoma haematobium and requiring mass treatment. This study investigates the reliability of school questionnaires to identify such schools and infected children within the context of a national school-based deworming programme in Kenya. METHODS: Between November 2008 and March 2009, 6182 children from 61 schools in Coast Province, Kenya were asked by an interviewer whether they had blood in urine or urinary schistosomiasis (kichocho), and their results were compared with results from microscopic examination of urine samples. Subsequently, in 2009, a school-based questionnaire survey for self-reported schistosomiasis was distributed by the Ministry of Education to all schools in Coast Province, and its results were compared against results from the parasitological survey. The questionnaire survey results were linked to a schools database and mapped. RESULTS: Prevalence of self-reported blood in urine was lower among girls than boys among all ages. The use of a 30% threshold of reported blood in urine was both highly sensitive (91.7%) and specific (100%) in identifying high (>50%) prevalence schools in Coast Province. Questionnaires were however less reliable in diagnosing S. haematobium infection in individuals, particularly among young girls. Comparable levels of reliability were observed when the questionnaire was distributed through the existing education systems and administered by class teachers. CONCLUSIONS: The results confirm that blood in urine questionnaires can be reliably used to target mass treatment with praziquantel at national scales. The mapped results of the Ministry of Education survey serve to describe the spatial variation of urinary schistosomiasis and identify schools requiring mass treatment
T-Cell Subsets Predict Mortality in Malnourished Zambian Adults Initiating Antiretroviral Therapy.
No full textThis is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are creditedTo estimate the prognostic value of T-cell subsets in Zambian patients initiating antiretroviral therapy (ART), and to assess the impact of a nutritional intervention on T-cell subsets.This work was supported by European and Developing Countries Clinical Trials Partnership grant # IP.2009.33011.004; trial foods were prepared and supplied by Nutriset, Malauney, Franc
Efficient genome engineering of Toxoplasma gondii using CRISPR/Cas9
No full textThis work was supported in part by NIH grant 1DP5OD017892 to S.LToxoplasma gondii is a parasite of humans and animals, and a model for other apicomplexans including Plasmodium spp., the causative agents of malaria. Despite many advances, manipulating the T. gondii genome remains labor intensive, and is often restricted to lab-adapted strains or lines carrying mutations that enable selection. Here, we use the RNA-guided Cas9 nuclease to efficiently generate knockouts without selection, and to introduce point mutations and epitope tags into the T. gondii genome. These methods will streamline the functional analysis of parasite genes and enable high-throughput engineering of their genomes.Peer reviewe
