Amino acid losses during hemodialysis with infusion of amino acids and glucose

Amino acid losses during hemodialysis with infusion of amino acids and glucose. This study evaluated the effects during hemodialysis of intravenous infusion of amino acids and glucose on plasma amino acid and glucose concentrations and amino acid losses. Eight men undergoing maintenance hemodialysis were each studied during two dialyses using glucose-free dialysate. During one hemodialysis, they were infused with 800ml of normal saline. During the other hemodialysis, they were infused with an equal volume of water which contained 39.5g of essential and non-essential free L-amino acids and 200g of d-glucose. The solutions were infused throughout the dialysis procedure into the drip chamber of the venous outflow from the dialyzer. Subjects were fasted from the night before until the end of hemodialysis, and the order of administration of the two solutions was determined randomly. Plasma essential, non-essential, and total amino acids fell significantly during the infusion of normal saline and rose during the administration of amino acids and glucose. Dialysate total-free amino acid losses averaged 8.2 ± 3.1SDg during the infusion of normal saline and 12.6 ± 3.6g with the administration of amino acids and glucose. These findings indicate that the intravenous infusion of amino acids and glucose during hemodialysis prevents a fall in plasma amino acid and glucose concentrations and leads to only a slight increase in the losses of free amino acids into dialysate. Because most of the infused amino acids are retained, this technique may be used during hemodialysis to avoid a net outflow of amino acids, minimize disruption of amino acid and glucose pools, and provide a nutritional supplement.Pertes en amino-acides au cours de l'hémodialyse avec perfusion d'acides aminés et de glucose. Cette étude a permis d'évaluer les effets de la perfusion intraveineuse d'acides aminés et de glucose pendant l'hémodialyse sur les concentrations plasmatiques d'acides aminés et de glucose, et les pertes d'acides aminés. Huit hommes en hémodialyse chronique ont chacun été étudiés pendant deux dialyses avec un dialysat sans glucose. Pendant une des dialyses ils étaient perfusés avec 800ml de soluté physiologique. Pendant l'hemodialyse autre ils ont infusé avec un égal volume d'eau contenant 39,5g de L-acides aminés libres essentiels ou non, et 200g de d-glucose. Les solutions étaient perfusées pendant la dialyse dans la tubulure veineuse venant du dialyseur. Les malades étaient à jeûn la nuit précédante et jusqu'à la fin de la dialyse, et l'ordre d'administration des deux solutions était déterminé au hasard. Les acides aminés plasmatiques totaux, essentiels et non essentiels ont significativement diminué pendant la perfusion de soluté physiologique, et se sont élevés pendant l'administration d'acides aminés et de glucose. Dans le dialysat, les pertes totales d'acides aminés libres étaient en moyenne de 8,2 ± 3,1g (ds) pendant la perfusion de soluté physiologique, et de 12,6 ± 3,6g lors de l'administration d'acides aminés et de glucose. Ces résultats indiquent que la perfusion intraveineuse d'acides aminés et de glucose au cours de la dialyse empêche la chute des acides aminés et du glucose plasmatiques et n'occasionne qu'une diminution minime des pertes en acides aminés libres dans le dialysat. Puisque la plupart des acides aminés perfusés est retenue, cette technique pourrait être utilisée pendant l'hémodialyse pour éviter une fuite nette d'acides aminés, pour minimiser la dissipation des réserves d'acides aminés et de glucose et pour apporter un supplément nutritif

A Field-Based Testing Protocol for Assessing Gross Motor Skills in Preschool Children: The Children\u27s Activity and Movement in Preschool Study Motor Skills Protocol

The purpose of this study was to develop a valid and reliable tool for use in assessing motor skills in preschool children in field-based settings. The development of the Children’s Activity and Movement in Preschool Study Motor Skills Protocol included evidence of its reliability and validity for use in field-based environments as part of large epidemiological studies. Following pilot work, 297 children (3–5 years old) from 22 preschools were tested using the final version of the Children’s Activity and Movement in Preschool Study Motor Skills Protocol and the Test of Gross Motor Development (2nd Edition). Reliability of the Children’s Activity and Movement in Preschool Study Motor Skills Protocol and interobserver reliability were determined using intraclass correlation procedures (intraclass correlation coefficients; ANOVA). Concurrent validity was assessed using Pearson correlation coefficients to compare the Children’s Activity and Movement in Preschool Study Motor Skills Protocol to the original Test of Gross Motor Development (2nd Edition). Results indicated that test reliability, interobserver reliability, and validity coefficients were all high, generally above R/r = .90. Significant age differences were found. Outcomes indicate that the Children’s Activity and Movement in Preschool Study Motor Skills Protocol is an appropriate tool for assessing motor development of 3-, 4-, and 5-year-old children in field-based settings that are consistent with large-scale trials

Diploma Privilege and the Constitution

The COVID-19 pandemic and resulting shutdowns are affecting every aspect of society. The legal profession and the justice system have been profoundly disrupted at precisely the time when there is an unprecedented need for legal services to deal with a host of legal issues generated by the pandemic, including disaster relief, health law, insurance, labor law, criminal justice, domestic violence, and civil rights. The need for lawyers to address these issues is great but the prospect of licensing new lawyers is challenging due to the serious health consequences of administering the bar examination during the pandemic. State Supreme Courts are actively considering alternative paths to licensure. One such alternative is the diploma privilege, a path to licensure currently used only in Wisconsin. Wisconsin\u27s privilege, limited to graduates of its two in-state schools, has triggered constitutional challenges never fully resolved by the lower courts. As states consider emergency diploma privileges to address the pandemic, they will face these unresolved constitutional issues. This Article explores those constitutional challenges and concludes that a diploma privilege limited to graduates of in-state schools raises serious Dormant Commerce Clause questions that will require the state to tie the privilege to the particular competencies in-state students develop and avenues they have to demonstrate those competencies to the state\u27s practicing bar over three years. Meeting that standard will be particularly difficult if a state adopts an in-state privilege on an emergency basis. States should consider other options, including privileges that do not prefer in-state schools. The analysis is important both for states considering emergency measures and for those that might restructure their licensing after the pandemic

The Bar Exam and the COVID-19 Pandemic: The Need for Immediate Action

The novel coronavirus COVID-19 has profoundly disrupted life in the United States. Among other challenges, jurisdictions are unlikely to be able to administer the July 2020 bar exam in the usual manner. It is essential, however, to continue licensing new lawyers. Those lawyers are necessary to meet current needs in the legal system. Equally important, the demand for legal services will skyrocket during and after this pandemic. We cannot close doors to the profession at a time when client demand will reach an all-time high.In this brief policy paper, we outline six licensing options for jurisdictions to consider for the Class of 2020. Circumstances will vary from jurisdiction to jurisdiction, but we hope that these options will help courts and regulators make this complex decision. These are unprecedented times: We must work together to ensure we do not leave the talented members of Class of 2020 on the sidelines when we need every qualified professional on the field to keep our justice system moving

Phase 2 study of canfosfamide in combination with pegylated liposomal doxorubicin in platinum and paclitaxel refractory or resistant epithelial ovarian cancer

<p>Abstract</p> <p>Background</p> <p>Canfosfamide is a novel glutathione analog activated by glutathione S-transferase P1-1. This study evaluated the safety and efficacy of canfosfamide in combination with pegylated liposomal doxorubicin (PLD) in patients with platinum resistant ovarian cancer. Patients with platinum resistant ovarian carcinoma and measurable disease received canfosfamide at 960 mg/m²in combination with PLD at 50 mg/m², intravenously day 1 in every 28 day cycles until tumor progression or unacceptable toxicities. The primary endpoints were objective response rate (ORR) and progression-free survival (PFS).</p> <p>Results</p> <p>Canfosfamide plus PLD combination therapy was administered at 960/50 mg/m², respectively. Thirty-nine patients received a median number of 4 cycles (range 1.0-18.0). The ORR was 27.8% (95% CI, 14.2-45.2) with a disease stabilization rate of 80.6% (95% CI, 64.0-91.8) in the evaluable population. The CA-125 marker responses correlated with the radiological findings of complete response or partial response. The median PFS was 6.0 months (95% CI, 4.2-7.9) and median survival was 17.8 months. The combination was well tolerated. Myelosuppression was managed with dose reductions and growth factor support. Grade 3 febrile neutropenia was observed in 2 patients (5.1%). Non-hematologic adverse events occurred at the expected frequency and grade for each drug alone, with no unexpected or cumulative toxicities.</p> <p>Conclusions</p> <p>Canfosfamide in combination with PLD is well tolerated and active in platinum and paclitaxel refractory or resistant ovarian cancer. A randomized phase 3 study was conducted based on this supportive phase 2 study.</p> <p>Trial Registration</p> <p>This study was registered at www.clinicaltrials.gov: NCT00052065.</p

Trefoil factor 2 rapidly induces interleukin 33 to promote type 2 immunity during allergic asthma and hookworm infection

The molecular mechanisms that drive mucosal T helper type 2 (T[subscript H]2) responses against parasitic helminths and allergens remain unclear. In this study, we demonstrate in mice that TFF2 (trefoil factor 2), an epithelial cell–derived repair molecule, is needed for the control of lung injury caused by the hookworm parasite Nippostrongylus brasiliensis and for type 2 immunity after infection. TFF2 is also necessary for the rapid production of IL-33, a T[subscript H]2-promoting cytokine, by lung epithelia, alveolar macrophages, and inflammatory dendritic cells in infected mice. TFF2 also increases the severity of allergic lung disease caused by house dust mite antigens or IL-13. Moreover, TFF2 messenger RNA expression is significantly increased in nasal mucosal brushings during asthma exacerbations in children. These experiments extend the biological functions of TFF2 from tissue repair to the initiation and maintenance of mucosal T[subscript H]2 responses

The Effect of the Earned Income Tax Credit in the District of Columbia on Poverty and Income Dynamics

Using unique longitudinal administrative tax panel data for the District of Columbia (DC), we assess the combined effect of the DC supplemental earned income tax credit (EITC) and the federal EITC on poverty and income dynamics within Washington, DC, from 2001 to 2011. The EITC in DC merits investigation, as the DC supplement to the federal credit is the largest in the nation. The supplemental DC EITC was enacted in 2000, and has been expanded from 10 percent of the federal credit in 2001 to 40 percent as of 2009. To implement the study, we estimate least squares models with 0/1 dependent variables to estimate the likelihood of net-EITC income above poverty and near-poverty thresholds. We also estimate the likelihood of earnings growth and income stabilization from the EITC. To identify the effect of the EITC, we exploit variation in the EITC subsidy rate from 2008 to 2009, when an additional EITC bracket of 45 percent was added for workers with three or more dependent children, up from 40 percent in the previous year for workers with two or more children. We also estimate a model examining the impact of city-level changes to the EITC. The structure and richness of our data enable us to control for tax filer fixed effects, an important innovation from many previous EITC studies. Overall, we find that the combined EITC raises the likelihood of net-EITC income above poverty and near poverty by as much as 9 percent, with the largest consistent effects accruing to single-parent families

Downregulation of RKIP Is Associated with Poor Outcome and Malignant Progression in Gliomas

Malignant gliomas are highly infiltrative and invasive tumors, which precludes the few treatment options available. Therefore, there is an urgent need to elucidate the molecular mechanisms underlying gliomas aggressive phenotype and poor prognosis. The Raf Kinase Inhibitory protein (RKIP), besides regulating important intracellular signaling cascades, was described to be associated with progression, metastasis and prognosis in several human neoplasms. Its role in the prognosis and tumourigenesis of gliomas remains unclear

Induction of the interleukin 6/ signal transducer and activator of transcription pathway in the lungs of mice sub-chronically exposed to mainstream tobacco smoke

<p>Abstract</p> <p>Background</p> <p>Tobacco smoking is associated with lung cancer and other respiratory diseases. However, little is known about the global molecular changes that precede the appearance of clinically detectable symptoms. In this study, the effects of mainstream tobacco smoke (MTS) on global transcription in the mouse lung were investigated.</p> <p>Methods</p> <p>Male C57B1/CBA mice were exposed to MTS from two cigarettes daily, 5 days/week for 6 or 12 weeks. Mice were sacrificed immediately, or 6 weeks following the last cigarette. High density DNA microarrays were used to characterize global gene expression changes in whole lung. Microarray results were validated by Quantitative real-time RT-PCR. Further analysis of protein synthesis and function was carried out for a select set of genes by ELISA and Western blotting.</p> <p>Results</p> <p>Globally, seventy nine genes were significantly differentially expressed following the exposure to MTS. These genes were associated with a number of biological processes including xenobiotic metabolism, redox balance, oxidative stress and inflammation. There was no differential gene expression in mice exposed to smoke and sampled 6 weeks following the last cigarette. Moreover, cluster analysis demonstrated that these samples clustered alongside their respective controls. We observed simultaneous up-regulation of <it>interleukin 6 </it>(<it>IL-6</it>) and its antagonist, <it>suppressor of cytokine signalling </it>(<it>SOCS3</it>) mRNA following 12 weeks of MTS exposure. Analysis by ELISA and Western blotting revealed a concomitant increase in total IL-6 antigen levels and its downstream targets, including phosphorylated signal transducer and activator of transcription 3 (Stat3), basal cell-lymphoma extra large (BCL-XL) and myeloid cell leukemia 1 (MCL-1) protein, in total lung tissue extracts. However, in contrast to gene expression, a subtle decrease in total SOCS3 protein was observed after 12 weeks of MTS exposure.</p> <p>Conclusion</p> <p>Global transcriptional analysis identified a set of genes responding to MTS exposure in mouse lung. These genes returned to basal levels following smoking cessation, providing evidence to support the benefits of smoking cessation. Detailed analyses were undertaken for IL-6 and its associated pathways. Our results provide further insight into the role of these pathways in lung injury and inflammation induced by MTS.</p