Artículos de revistas: "Down titration"

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Shafer, Steven L. y Donald R. Stanski. "The Titration Paradox Turns Pharmacology Upside Down". Clinical Pharmacology & Therapeutics 110, n.º 2 (14 de abril de 2021): 292–93. http://dx.doi.org/10.1002/cpt.2235.

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van der Maas, Aatke, Wietske Kievit, Bart J. F. van den Bemt, Frank H. J. van den Hoogen, Piet L. van Riel y Alfons A. den Broeder. "Down-titration and discontinuation of infliximab in rheumatoid arthritis patients with stable low disease activity and stable treatment: an observational cohort study". Annals of the Rheumatic Diseases 71, n.º 11 (13 de abril de 2012): 1849–54. http://dx.doi.org/10.1136/annrheumdis-2011-200945.

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Down-titration, or discontinuing infliximab, has proven to be feasible in RA patients. Therefore, our local treatment protocol includes tapering infliximab dose. This observational study describes the prevalence of successful down-titration in daily clinical practice and its effect on costs and quality of life (QoL).MethodsInfliximab was down-titrated with 25% of the original dose (3 mg/kg) every 8–12 weeks without interval change until discontinuation or flare in all RA patients with stable low 28-joint disease activity score (DAS28) and stable treatment for >6 months. During 1 year DAS28, RA medication, outpatient clinic visits, RA related absenteeism and EuroQoL5D (European QoL questionnaire, EQ5D) were documented. Prevalence of successful down-titration and changes in DAS28, QoL and costs were described.ResultsIn 16% (95% CI 6 to 26) and 45% (95% CI 31 to 59), respectively, infliximab could be discontinued or down-titrated. Mean infliximab dose decreased significantly from 224 mg (95% CI 212 to 236 mg) at start, to 130 mg (95% CI 105 to 154 mg) after 1 year. Median DAS28 increased from 2.5 (p25–75=2.0–2.9) to 2.8 (2.2–3.6) (p=0.002). Extra corticosteroids were given in 8% of the visits. Disease modifying antirheumatic drugs were seldom changed. There was no statistical difference in QoL after down-titration. Mean reduction in the costs was €3474 (95% CI 2457 to 4492) per patient.ConclusionIn the majority of patients with stable low DAS28 and stable treatment, infliximab can be down-titrated or discontinued, which results in a considerable reduction in costs without influencing QoL.

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Birch, J. "Micro-titration of depot neuroleptic dosages". Psychiatric Bulletin 20, n.º 11 (noviembre de 1996): 660–61. http://dx.doi.org/10.1192/pb.20.11.660.

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Depot neuroleptic treatments can be compromised by side-effects unacceptable to users or, more seriously, by tardive dyskinesia (TD). Neuroleptic dosages can be lowered to increase acceptability and decrease the Incidence of TD, but with a greater likelihood of relapse. One argument proposes that many patients changing to lower dosages break down because withdrawal from a neuroleptic is stressful in itself. Research suggests that withdrawal regimes should be radically cautious. A computer tool is offered which can aid clinicians in calculating small reductions.

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Omodeo, Pinuccia. "Down-titration of omalizumab in a patient with chronic spontaneous urticaria". Journal of Dermatological Treatment 29, sup4 (14 de diciembre de 2018): 12–13. http://dx.doi.org/10.1080/09546634.2018.1529379.

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Caffrey, Aisling R. y Eric P. Borrelli. "The art and science of drug titration". Therapeutic Advances in Drug Safety 11 (enero de 2020): 204209862095891. http://dx.doi.org/10.1177/2042098620958910.

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A “one-size-fits-all” approach has been the standard for drug dosing, in particular for agents with a wide therapeutic index. The scientific principles of drug titration, most commonly used for medications with a narrow therapeutic index, are to give the patient adequate and effective treatment, at the lowest dose possible, with the aim of minimizing unnecessary medication use and side effects. The art of drug titration involves the interplay of scientific drug titration principles with the clinical expertise of the healthcare provider, and an individualized, patient-centered partnership between the provider and the patient to review the delicate balance of perceived benefits and risks from both perspectives. Drug titration may occur as up-, down-, or cross-titration depending on whether the goal is to reach or maintain a therapeutic outcome, decrease the risk of adverse effects, or prevent withdrawal/discontinuation syndromes or recurrence of disease. Drug titration introduces additional complexities surrounding the conduct of clinical trials and real-world studies, confounding our understanding of the true effect of medications. In clinical practice, wide variations in titration schedules may exist due to a lack of evidence and consensus on titration approaches that achieve an optimal benefit-harm profile. Further, drug titration may be challenging for patients to follow, resulting in suboptimal adherence and may require increased healthcare-related visits and coordination of care amongst providers. Despite the challenges associated with drug titration, it is a personalized approach to drug dosing that blends science with art, and with supportive real-world outcomes-based evidence, can be effective for optimizing pharmacotherapeutic outcomes and improving drug safety.

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Soldatov, V. S., T. A. Korshunova, E. G. Kosandrovich y P. V. Nesteronok. "Titration of chelating fibrous sorbent in the presence of complex-forming divalent cations". Proceedings of the National Academy of Sciences of Belarus, Chemical Series 57, n.º 3 (5 de septiembre de 2021): 263–69. http://dx.doi.org/10.29235/1561-8331-2021-57-2-263-269.

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Titration curves of H-forms of the fibrous chelating sorbent with iminodiacetic groups based on industrial polyacrylonitrile fiber Nitron with potassium hydroxide in 1M KCl solution in the presence of Ni2+, Co2+, Cu2+ and Ca2+ chlorides were obtained. The method used made it possible to simultaneously measure the pH of the solution and the concentration of the divalent cation at each point of the titration curve. From these data, the dependences of their sorption values on the pH of the equilibrium solution were calculated. The curves of direct and back titration practically coincided in all cases. As the pH changed during titration, precipitation was observed at pH values of precipitation of the corresponding hydroxides. In this case, the increase in pH was suspended or greatly slowed down by adding alkali to the titration cell. The formation of a precipitate occurred mainly in a solution for Co2+ and Ni2+ (pH 8), when the ion exchanger was saturated with a metal ion. In the case of Cu2+ (precipitate formation pH 4), Cu2+ sorption occurs at both lower and higher pH due to ionization of carboxyl groups and partial dissolution of the precipitate. In all cases, the maximum sorption of Ni2+, Co2+, Cu2+, Ca2+ corresponded to the formation of sorption complexes of the R–N(CH2COO-)2Me2+ type.

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Laires, Pedro A., Jackson Tang, Chun Po Steve Fan, Zhiyi Li, Ying Qiu y Kristy Iglay. "Impact of hypoglycemic events and HbA1c level on sulfonylurea discontinuation and down-titration". Expert Review of Pharmacoeconomics & Outcomes Research 17, n.º 2 (30 de junio de 2016): 213–20. http://dx.doi.org/10.1080/14737167.2016.1203259.

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Al Kasab, Sami, Rachael A. Dawson, Jorge L. Jaramillo y Jonathan J. Halford. "Correlation of seizure frequency and medication down-titration rate during video-EEG monitoring". Epilepsy & Behavior 64 (noviembre de 2016): 51–56. http://dx.doi.org/10.1016/j.yebeh.2016.08.026.

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Piaserico, S., P. Gisondi, C. Simone, E. Marinello, A. Conti, P. Amerio y A. Peserico. "Down-titration of Adalimumab and Etanercept in Psoriatic Patients: A Multicentre Observational Study". Acta Dermato Venereologica 96, n.º 2 (2016): 251–52. http://dx.doi.org/10.2340/00015555-2209.

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Ioachimescu, Adriana Gabriela, Richard Joseph Auchus, Wenyu Huang, Joanna L. Spencer-Segal, Kevin Choong Ji Yuen, Kelley C. Dacus, William Henry Ludlam et al. "LBMON177 Dosing And Titration Of Osilodrostat In A Real-world Cohort Of US Patients With Endogenous Cushing's Disease: Analysis Of The ILLUSTRATE Study". Journal of the Endocrine Society 6, Supplement_1 (1 de noviembre de 2022): A473—A474. http://dx.doi.org/10.1210/jendso/bvac150.983.

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Abstract Background Osilodrostat, a potent oral inhibitor of 11β-hydroxylase, demonstrated efficacy in normalizing urinary free cortisol (UFC) in Cushing's disease (CD) patients; however, information describing its use in clinical practice is limited. We present osilodrostat dosing and titration information from a real-world cohort of endogenous Cushing's syndrome (CS) patients, focused on CD. Methods ILLUSTRATE, a retrospective chart review study analyzed confirmed endogenous CS patients who initiated osilodrostat treatment May 1, 2020 - October 29, 2021. Forty-two adult patients with endogenous CS and a prescription for osilodrostat were included in this real-world study. We describe the experience with initial osilodrostat dose, dose titration, and persistence in the CD subset (n=34, 81%). Results In patients with CD (n=34) the mean total daily starting dose was 3.4 mg (SD 1; median 4 mg; range 1-6 mg/day). Twenty-one patients (62%) were initiated on 2 mg BID, 9 (27%) on 1 mg BID, and 1 each (3%) on 1 mg QD, 2 mg QD, 3 mg BID and 4 mg QD. In CD patients with multiple documented clinical encounters (n=26), 16 initiated at 4 mg/day, of which the dose was interrupted or down-titrated in 4 patients (25%) within 71 days of treatment initiation; 2/4 of these patients experienced hypocortisolism related symptoms and permanently discontinued. Five of the 16 patients (31%) were maintained on 4 mg/day throughout the observation period, with a mean (SD) treatment duration of 273 (median 278 days; SD 92) days. Seven of 16 patients (44%) had a dose up-titration; in 6/7 patients, initial dose increase was incremental (1-2 mg BID), and the mean (SD) time to up-titration was 78 (SD 25; median 83; range 40-108) days. In the 10 of 26 CD patients who initiated therapy at <2 mg BID, 6 (60%) did not require dose reduction or interruption, all of which had up-titration in small increments (1-2 mg/day) and/or first titration at ≥80 days. Treatment persistence for those enrolled ≥ 6 months prior to study end was 95.8%, mean (SD) duration of therapy was 339.2 (106.8) days. Osilodrostat was generally well tolerated. Symptoms related to decreased cortisol levels were reported in 10/26 patients (38%), including 3 patients with adrenal insufficiency and 7 patients with glucocorticoid withdrawal symptoms. Conclusion ILLUSTRATE captures real-world US data describing the experience of CD patients treated with osilodrostat. Importantly, one-third (11/34) of patients were initiated on a dose lower than 4 mg/day (lower than starting dose previously used in clinical trials). Of 16 patients initiated at 4 mg/day, 4 (25%) required interruption or down-titration and 5 (31%) remained on the initial dose throughout the observation period. Overall, consistent with prior research data, patients with a gradual dose up-titration (i. e., prolonged titration interval) tended to have greater persistence with therapy. There were no new safety findings. Presentation: Monday, June 13, 2022 12:30 p.m. - 2:30 p.m.

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Lojo, L., G. Bonilla, D. Peiteado, A. Villalba, C. Plasencia, L. Nuño, A. Balsa y E. Martín-Mola. "THU0216 Down-Titration and Discontinuation of Infliximab, Adalimumab and Etanercept in Established Rheumatoid Arthritis". Annals of the Rheumatic Diseases 72, Suppl 3 (junio de 2013): A237.3—A237. http://dx.doi.org/10.1136/annrheumdis-2013-eular.744.

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Lau, Chak Sing, Allan Gibofsky, Nemanja Damjanov, Sadiq Lula, Lisa Marshall, Heather Jones y Paul Emery. "Down-titration of biologics for the treatment of rheumatoid arthritis: a systematic literature review". Rheumatology International 37, n.º 11 (29 de agosto de 2017): 1789–98. http://dx.doi.org/10.1007/s00296-017-3780-8.

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Kozlov, Guennadi, Long Nguyen, Tong Lin, Gregory De Crescenzo, Morag Park y Kalle Gehring. "Structural Basis of Ubiquitin Recognition by the Ubiquitin-associated (UBA) Domain of the Ubiquitin Ligase EDD". Journal of Biological Chemistry 282, n.º 49 (25 de septiembre de 2007): 35787–95. http://dx.doi.org/10.1074/jbc.m705655200.

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EDD (or HYD) is an E3 ubiquitin ligase in the family of HECT (homologous to E6-AP C terminus) ligases. EDD contains an N-terminal ubiquitin-associated (UBA) domain, which is present in a variety of proteins involved in ubiquitin-mediated processes. Here, we use isothermal titration calorimetry (ITC), NMR titrations, and pull-down assays to show that the EDD UBA domain binds ubiquitin. The 1.85Å crystal structure of the complex with ubiquitin reveals the structural basis of ubiquitin recognition by UBA helices α1 and α3. The structure shows a larger number of intermolecular hydrogen bonds than observed in previous UBA/ubiquitin complexes. Two of these involve ordered water molecules. The functional importance of residues at the UBA/ubiquitin interface was confirmed using site-directed mutagenesis. Surface plasmon resonance (SPR) measurements show that the EDD UBA domain does not have a strong preference for polyubiquitin chains over monoubiquitin. This suggests that EDD binds to monoubiquitinated proteins, which is consistent with its involvement in DNA damage repair pathways.

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Singh, Haramandeep, Danielle Hyman, Gregory Parks, Abby Chen, Beth Baldys, Diane Ito y Michael Thorpy. "484 Solriamfetol Titration & AdministRaTion (START): Physician titration strategies in a hypothetical patient with narcolepsy". Sleep 44, Supplement_2 (1 de mayo de 2021): A191. http://dx.doi.org/10.1093/sleep/zsab072.483.

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Abstract Introduction Solriamfetol (Sunosi®), a dopamine/norepinephrine reuptake inhibitor, is approved (US and EU) to treat excessive daytime sleepiness (EDS) in adults with narcolepsy (75–150 mg/day) or obstructive sleep apnea (OSA) (37.5–150 mg/day). Patient characteristics, comorbidities, and other EDS medications can influence treatment strategies. To understand factors physicians consider when initiating solriamfetol, this study analyzed titration strategies for a hypothetical patient. Methods This virtual, descriptive, cross-sectional, qualitative survey enrolled US-based physicians treating patients with EDS due to OSA and/or narcolepsy. Responses to 4 open-ended questions regarding a hypothetical patient were recorded. Patient scenario: 32-year-old woman with narcolepsy (Epworth Sleepiness Scale score=8) using an amphetamine stimulant (35 mg/day) and sodium oxybate (6 g/night) for 6 months and occasionally experiencing non-use-limiting but bothersome adverse events (AEs) with the stimulant. Content analysis of the recordings identified themes in the responses; a trained linguist captured language choices/patterns. Results Twenty-six physicians (neurologists, n=7 [27%]; internists/family practitioners, n=7 [27%]; pulmonologists, n=6 [23%]; psychiatrists, n=5 [19%]; otolaryngologists, n=1 [4%]) representing 781 patients on stable solriamfetol doses participated; 19 (73%) were board-certified in sleep disorders. Physicians had been treating narcolepsy a mean 15.7±6.6 years. Most (21 [81%]) thought the patient appropriate for solriamfetol, 3 (12%) thought not appropriate, and 2 (8%) thought appropriateness depended on other factors. Sixteen physicians (62%) suggested adjusting her stimulant, 3 (12%) the stimulant and sodium oxybate, and 1 (4%) neither. Nineteen (73%) would titrate solriamfetol per the label, with 13 (50%) aiming for 75 mg/day and 8 (31%) for 150 mg/day. Physicians emphasized stopping the stimulant before starting solriamfetol: 10 (39%) would taper down before starting solriamfetol, 7 (27%) while starting solriamfetol, and 1 (4%) while aiming to eventually switch; 8 (31%) would discontinue abruptly. Nineteen physicians (73%) would not change their approach if the stimulant dose were 60 mg/day. Most clinicians would change their approach if AEs occurred while starting solriamfetol by taking a slower or more gradual approach, while some would titrate off the stimulant more aggressively. Conclusion Physicians considered existing medications and potential AEs in their titration strategy when initiating solriamfetol. Support (if any) Jazz Pharmaceuticals

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Kalousková, Radka, Lenka Malinová, Václava Benešová y Jiří Brožek. "Evaluation of the Stability of PVC Book Covers". Chemické listy 116, n.º 6 (10 de junio de 2022): 381–87. http://dx.doi.org/10.54779/chl20220381.

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When determining the state of deterioration of book covers made of softened polyvinylchloride, which is essential for the choice of conservation strategy, we are limited by the sample amount available for analytical evaluation. Infrared spectroscopy, as opposed to potentiometric titration, not always allows to unambiguously prove the decrease of sample thermal stability, nor the depletion of the stabilizer, the presence of which slows down dehydrochlorination and neutralizes released hydrogen chloride. For unplastized PVC samples, the time loss of weight determined by thermogravimetric analysis at 180 °C correlates with the amount of released hydrogen chloride obtained from potentiometric titration. The stability of the packages is closely linked to the history and handling of the books. It can be assumed that, with careful use and storing in the library depositories, book covers will remain functional for several decades.

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Saadaoui, K., H. Sahli, S. Boussaid, J. Samia, R. Sonia, C. Elhem y E. Mohammed. "AB0236 DOWN-TITRATION STRATEGY OF TUMOR NECROSIS FACTOR-INHIBITOR AGENTS FOR RHEUMATOID ARTHRITIS IN TUNISIA". Annals of the Rheumatic Diseases 80, Suppl 1 (19 de mayo de 2021): 1144.1–1144. http://dx.doi.org/10.1136/annrheumdis-2021-eular.3804.

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Background:Tumor necrosis factor (TNF) blocking agents are effective in treating rheumatoid arthritis, but they are associated with several adverse effects and high costs. Some studies have assessed the effectiveness of down-titration compared with continuation of standard dose.Objectives:The aim of our study is to assess dose tapering in Tunisia.Methods:A retrospective study including 170 rheumatoid arthritis patients treated by TNF blocker agent and with either low disease activity or remission (ACR/EULAR criteria). Two groups were compared, in the first group (G1) the interval of TNFi administration was extended, in the second group (G2) the standard dose and rhythm of administration were maintained.Results:The TNFi tapering group (G1) included 96 persons whereas the group having the same drug administration rhythm (G2) included 74 case. The baseline age of the down-dosing drug group was 56.6 ± 12.6 years versus 52.9 ± 11.6 years in the other group (p = 0.046) and the average disease duration were respectively 12.3 ± 7.2 years versus 11.2 ± 6 years (p = 0.346). Women represented 88.5% in G1 versus 93% in G2 (p = 0.298). Rheumatoid Factors and ACPA were positive respectively in (85.5% versus 83.8; p = 0.748) and (76.4% versus 67.8%; p= 0.309). Etanercept, adalimumab, certolizumab pegol and infliximab were respectively used in 84.4%, 9.4%, 4.2% and 2.1% cases (G1), whereas they were used in 48.6%, 16.2%, 27% and 8.1% cases in the second group (G2). In the TNFi down dosing group, methotrexate was associated to TNFi in 74% cases while 71.6% of patient received methotrexate in the standard rhythm of administration group (p = 0.734). Corticosteroids were used by 40.6% of patients in G1 vs. 56.8% of patients in G2 (p = 0.037). The average DAS28 at baseline was 5.91 ± 0.81 (G1) versus 5.95 ± 0.80 (G2) (p = 0.759). There was no statistically significant difference between the two groups for rates of TNFi withdrawal (p = 0.798). In fact, TNFi was interrupted due to inefficacy for 17 patients (17.7%) in the down-dosing group versus 12 patients (16.2%) in the other group.Conclusion:Our study add evidence that TNFi drugs tapering could be equivalent to maintenance strategy. This could be beneficial to decrease the risk of adverse effect or reduce costs. Further studies are needed to confirm those results and identify patients who could benefit of TNFi administration rhythm step-down.Disclosure of Interests:None declared

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Martens, Pieter, Frederik H. Verbrugge, Levinia Boonen, Petra Nijst, Matthias Dupont y Wilfried Mullens. "Value of routine investigations to predict loop diuretic down-titration success in stable heart failure". International Journal of Cardiology 250 (enero de 2018): 171–75. http://dx.doi.org/10.1016/j.ijcard.2017.10.018.

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Reddel, Helen K., Peter G. Gibson, Matthew J. Peters, Peter A. B. Wark, Ingrid B. Sand, Camilla M. Hoyos y Christine R. Jenkins. "Down-titration from high-dose combination therapy in asthma: Removal of long-acting β2-agonist". Respiratory Medicine 104, n.º 8 (agosto de 2010): 1110–20. http://dx.doi.org/10.1016/j.rmed.2010.04.003.

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Titova, Оlga, Zoia Hrushak, Tetiana Kravchuk, Valerii Yefymenko y Mariia Maksumiuk. "GENERATION OF SYNTHETICAL MEDICAL DATA BY MDR-ANALYSIS". Proceedings of the National Aviation University 87, n.º 2 (27 de julio de 2021): 37–47. http://dx.doi.org/10.18372/2306-1472.87.15686.

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Purpose: The purpose of this article is to determine the dependence of the rate of gel formation on the type of reagent-inhibitor of the gel formation process, and to study the kinetic dependences of gel formation of silicate compositions in the presence of compounds that regulate the rate of gel formation. Research methods: Direct and reverse titration, potentiometric titration, pH-metry, determination of the dynamic viscosity on a rotational viscometer, axial compression method to determine the elastic modulus were used to study the possibility of using chemical reagents as gelation inhibitors. Results: The possibility of using inorganic and organic additives to slow down the gel formation process and the effect of these additives on the strength of the gel, their thermodynamic parameters have been researched. Discussion: The adding of organic acids into the silicate composition as "crosslinking agents" slows down the gel formation process, while replacing hydrochloric acid with other gel acids that slow down the gel formation process does not lead to a decrease in the strength characteristics of these systems compared to the standard. It was found that with an increase in the gelation time, the strength of the gels decreases, and the syneresis increases; the adding of inhibitor additives insignificantly worsens the filterability of silicate compositions, which in general have bad filterability, leading to an increase in resistance during filtration at the inlet section of the sample. Observations have shown that the addition of additives-inhibitors does not affect the thermal stability of gels, regardless of the additives' nature.

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Schreiber, S. y P. Scheid. "Gastric mucus of the guinea pig: proton carrier and diffusion barrier". American Journal of Physiology-Gastrointestinal and Liver Physiology 272, n.º 1 (1 de enero de 1997): G63—G70. http://dx.doi.org/10.1152/ajpgi.1997.272.1.g63.

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Proton transport with the gastric mucus was investigated in the guinea pig in vitro by use of three experimental series. In series I, pH profiles were obtained in the mucus and mucosa of a gastric explant with fine-tipped double-barreled microelectrodes. With a luminal pH of 1.8, pH increased across this layer to approximately 6 at the epithelial surface. Thickness of the gastric mucous gel layer increased continuously by 170 +/- 100 microns/h in the unstimulated and by 450 +/- 120 microns/h in the histamine-stimulated preparation (means +/- SD). In series II, fresh guinea pig gastric mucus was obtained from the gastric mucosa and titrated at 10 degrees C from pH 6.5 to 0.7, followed by an incubation period of 30 min at 37 degrees C. During this incubation period, a spontaneous acidic shift was observed, corresponding to a proton release from the mucus of 130 +/- 19 mM. This proton release could be blocked by the pepsin inhibitor pepstatin and was not observed when titrating down to only pH 3. Buffer values calculated as the mean slope of the titration curves in the pH range of 7 to 3 averaged 40 mM/pH unit. In series III, when titration was repeated with purified porcine mucin, no proton release was observed during incubation at pH 1.0, unless pepsinogen (375 U/ml) had been added before titration. Proton release during incubation at pH 1.0 and 37 degrees C in the presence of pepsinogen averaged 50 mM. The data suggest that protons secreted by the gastric mucosa are buffered by the continuously secreted mucus and transported, bound to the proteins of the mucus, toward the gastric lumen. During this transport, pepsinogen is converted within the mucus to pepsin. Pepsin modifies the buffering properties of the mucus, whereby protons are released from the protein binding. Thus the mucus forms a vehicle for proton transport toward the gastric lumen while, at the same time, constituting a diffusion barrier to prevent proton backdiffusion toward the gastric epithelium.

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HAMMOND, J. "D63 Successful maintenance of blood pressure control in 79% of patients following down titration of ramipril". American Journal of Hypertension 10, n.º 4 (abril de 1997): 120A. http://dx.doi.org/10.1016/s0895-7061(97)89092-9.

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Kempfle, J. S., G. R. Diercks, T. B. Kinane, B. Skotko, D. Keamy y C. J. Hartnick. "0769 Polysomnographic Analysis Of Post-stimulation Titration In Children With Down Syndrome And Hypoglossal Nerve Implant". Sleep 41, suppl_1 (abril de 2018): A286. http://dx.doi.org/10.1093/sleep/zsy061.768.

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Pi, Keng-Shuo, Daria Bortolotti, Yurou Sang, Giovanna Schiuma, Silvia Beltrami, Sabrina Rizzo, Alessandra Bortoluzzi et al. "Studying the Interactions of U24 from HHV-6 in Order to Further Elucidate Its Potential Role in MS". Viruses 14, n.º 11 (28 de octubre de 2022): 2384. http://dx.doi.org/10.3390/v14112384.

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A number of studies have suggested that human herpesvirus 6A (HHV-6A) may play a role in multiple sclerosis (MS). Three possible hypotheses have been investigated: (1) U24 from HHV-6A (U24-6A) mimics myelin basic protein (MBP) through analogous phosphorylation and interaction with Fyn-SH3; (2) U24-6A affects endocytic recycling by binding human neural precursor cell (NPC) expressed developmentally down-regulated protein 4-like WW3* domain (hNedd4L-WW3*); and (3) MS patients who express Killer Cell Immunoglobulin Like Receptor 2DL2 (KIR2DL2) on natural killer (NK) cells are more susceptible to HHV-6 infection. In this contribution, we examined the validity of these propositions by investigating the interactions of U24 from HHV-6B (U24-6B), a variant less commonly linked to MS, with Fyn-SH3 and hNedd4L-WW3* using heteronuclear single quantum coherence (HSQC) nuclear magnetic resonance (NMR) titrations and isothermal titration calorimetry (ITC). In addition, the importance of phosphorylation and the specific role of U24 in NK cell activation in MS patients were examined. Overall, the findings allowed us to shed light into the models linking HHV-6 to MS and the involvement of U24.

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Asis, Aristotle y Kevin Kaplan. "1228 A CASE OF PULMONARY HYPERTENSION AND SEVERE OBSTRUCTIVE SLEEP APNEA IN A PEDIATRIC PATIENT WITH DOWN SYNDROME". Sleep 43, Supplement_1 (abril de 2020): A469. http://dx.doi.org/10.1093/sleep/zsaa056.1222.

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Abstract Introduction Children with Down syndrome (DS) are at risk for obstructive sleep apnea (OSA) and related health consequences. Adherence to treatment plans, especially positive airway pressure (PAP), can be difficult for people with DS. We present a case of a pediatric patient with DS who developed pulmonary arterial hypertension (PAH) due to poor adherence of OSA therapy. Report of Case A 4-year-old male with a past medical history of DS was diagnosed with severe OSA and hypoventilation at 18 months of age – AHI 27, (oAHI 27), CO2 above 50 mmHg for 53.2% of total sleep time (TST)). A titration study showed that on a bi-level pressure (BPAP) of 11/6 cm H2O his OSA was improved – AHI 5.9 (oAHI 3.7), O2 nadir of 93%. The family attempted PAP at home but discontinued after 2 weeks. He underwent an adenoidectomy at 22 months of age and tonsillectomy and repeat adenoidectomy at 40 months of age. Patient presents to the emergency center with respiratory distress. Chest films showed cardiomegaly. Echocardiogram revealed evidence of worsening PAH (tricuspid regurgitation of 3.5-3.8 m/s and flattening of the interventricular septum). He was admitted to the pediatric intensive care unit for further management of his PAH attributed to his underlying uncorrected OSA and hypoventilation. Repeat polysomnogram showed continue severe OSA and hypoventilation – AHI 30.3 (oAHI 30.3) CO2 above 50 mmHg for 89% of TST. Repeat titration study showed that a pressure of 11/7 cm H2O improved his OSA– AHI 6.4 (oAHI 6.4) CO2 max of 52 mmHg. Treatment with BPAP was initiated prior to discharge. Repeat echocardiogram 2 months after admission showed improvement of the PAH while on BPAP without additional vasoactive drug therapy. Conclusion Children with DS are at high risk for OSA. Although treatment can be difficult, proper management of the OSA essential to preventing potential serious health consequences.

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Iglay, Kristy, Ying Qiu, Chun-Po Steve Fan, Zhiyi Li, Jackson Tang y Pedro Laires. "Risk factors associated with treatment discontinuation and down-titration in type 2 diabetes patients treated with sulfonylureas". Current Medical Research and Opinion 32, n.º 9 (13 de junio de 2016): 1567–75. http://dx.doi.org/10.1080/03007995.2016.1190325.

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Bianchi, Stefano y Giuseppe Regolisti. "Pivotal clinical trials, meta-analyses and current guidelines in the treatment of hyperkalemia". Nephrology Dialysis Transplantation 34, Supplement_3 (1 de diciembre de 2019): iii51—iii61. http://dx.doi.org/10.1093/ndt/gfz213.

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Abstract Hyperkalemia (HK) is the most common electrolyte disturbance observed in patients with advanced stages of chronic kidney disease (CKD), is a potentially life-threatening clinical condition due to an increased risk of fatal arrhythmias, and strongly impacts the quality of life and prognosis of CKD patients. Moreover, while renin–angiotensin–aldosterone system inhibitors (RAASIs) represent the most cardio-nephro-protective drugs used in clinical practice, the treatment with these drugs per se increases serum potassium (sK) values, particularly when heart failure and diabetes mellitus coexist. In fact, the onset or recurrence of HK is frequently associated with not starting, down-titrating or withdrawing RAASIs, and is an indication to begin renal replacement treatment in end-stage renal disease. Current strategies aimed at preventing and treating chronic HK are still unsatisfactory, as evidenced by the relatively high prevalence of HK also in patients under stable nephrology care, and even in the ideal setting of randomized clinical trials. Indeed, dietary potassium restriction, the use of sodium bicarbonate or diuretics, the withdrawal or down-titration of RAASIs, or the administration of old potassium binders, namely sodium polystyrene sulphonate and calcium polystyrene sulphonate, have limited efficacy and are poorly tolerated; therefore, these strategies are not suitable for long-term control of sK. As such, there is an important unmet need for novel therapeutic options for the chronic management of patients at risk for HK. The development of new potassium binders may change the treatment landscape in the near future. This review summarizes the current evidence on the treatment of chronic HK in cardio-renal patients.

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Nakayama, Naomi, Gyosuke Sakashita, Takashi Nagata, Naohiro Kobayashi, Hisashi Yoshida, Sam-Yong Park, Yuko Nariai et al. "Nucleus Accumbens-Associated Protein 1 Binds DNA Directly through the BEN Domain in a Sequence-Specific Manner". Biomedicines 8, n.º 12 (14 de diciembre de 2020): 608. http://dx.doi.org/10.3390/biomedicines8120608.

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Nucleus accumbens-associated protein 1 (NAC1) is a nuclear protein that harbors an amino-terminal BTB domain and a carboxyl-terminal BEN domain. NAC1 appears to play significant and diverse functions in cancer and stem cell biology. Here we demonstrated that the BEN domain of NAC1 is a sequence-specific DNA-binding domain. We selected the palindromic 6 bp motif ACATGT as a target sequence by using a PCR-assisted random oligonucleotide selection approach. The interaction between NAC1 and target DNA was characterized by gel shift assays, pull-down assays, isothermal titration calorimetry (ITC), chromatin-immunoprecipitation assays, and NMR chemical shifts perturbation (CSP). The solution NMR structure revealed that the BEN domain of human NAC-1 is composed of five conserved α helices and two short β sheets, with an additional hitherto unknown N-terminal α helix. In particular, ITC clarified that there are two sequential events in the titration of the BEN domain of NAC1 into the target DNA. The ITC results were further supported by CSP data and structure analyses. Furthermore, live cell photobleaching analyses revealed that the BEN domain of NAC1 alone was unable to interact with chromatin/other proteins in cells.

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Della Ducata, Daniela, Jan Jaehrling, Cornelia Hänel, Marion Satzger, Meike Wolber, Ralf Ostendorp, Stefan Pabst y Bodo Brocks. "Solution Equilibrium Titration for High-Throughput Affinity Estimation of Unpurified Antibodies and Antibody Fragments". Journal of Biomolecular Screening 20, n.º 10 (15 de julio de 2015): 1256–67. http://dx.doi.org/10.1177/1087057115595002.

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The generation of therapeutic antibodies with extremely high affinities down to the low picomolar range is today feasible with state-of-the art recombinant technologies. However, reliable and efficient identification of lead candidates with the desired affinity from a pool of thousands of antibody clones remains a challenge. Here, we describe a high-throughput procedure that allows reliable affinity screening of unpurified immunoglobulin G or antibody fragments. The method is based on the principle of solution equilibrium titration (SET) using highly sensitive electrochemiluminescence as a readout system. Because the binding partners are not labeled, the resulting KD represents a sound approximation of the real affinity. For screening, diluted bacterial lysates or cell culture supernatants are equilibrated with four different concentrations of a soluble target molecule, and unbound antibodies are subsequently quantified on 384-well Meso Scale Discovery (MSD) plates coated with the respective antigen. For determination of KD values from the resulting titration curves, fit models deduced from the law of mass action for 1:1 and 2:1 binding modes are applied to assess hundreds of interactions simultaneously. The accuracy of the method is demonstrated by comparing results from different screening campaigns from affinity optimization projects with results from detailed affinity characterization.

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Verbrugge, Frederik H., Pieter Martens, Levinia Boonen, Petra Nijst, David Verhaert, Patrick Noyens, Philip De Vusser, Matthias Dupont, W. H. Wilson Tang y Wilfried Mullens. "Loop diuretic down-titration in stable chronic heart failure is often achievable, especially when urinary chloride concentration is low". Acta Cardiologica 73, n.º 4 (3 de octubre de 2017): 335–41. http://dx.doi.org/10.1080/00015385.2017.1385152.

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30

Linde, Cecilia, Phil McEwan, Ameet Bakhai, Hans Furuland, Marc Evans, Daniel Ayoubkhani, Susan Grandy, Eirini Palaka y Lei Qin. "FP337RELATIONSHIP BETWEEN HYPERKALAEMIA AND DOWN-TITRATION OR DISCONTINUATION OF RENIN-ANGIOTENSIN-ALDOSTERONE SYSTEM INHIBITORS IN UK PATIENTS WITH CKD". Nephrology Dialysis Transplantation 33, suppl_1 (1 de mayo de 2018): i145. http://dx.doi.org/10.1093/ndt/gfy104.fp337.

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31

Lee, T. H., J. G. Nam, O. L. Park y E. M. Lee. "Effective CPAP changes related to sleep stage and body position in osa during up and down-titration: experimental study". Sleep Medicine 64 (diciembre de 2019): S219—S220. http://dx.doi.org/10.1016/j.sleep.2019.11.614.

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32

Nalamachu, MD, Srinivas, Martin Hale, MD y Arif Khan, MD. "Hydromorphone extended release for neuropathic and non-neuropathic/nociceptive chronic low back pain: A post hoc analysis of data from a randomized, multicenter, double-blind, placebo-controlled clinical trial". Journal of Opioid Management 10, n.º 5 (1 de septiembre de 2014): 311. http://dx.doi.org/10.5055/jom.2014.0221.

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Objective: The aim of this study was to determine the efficacy and tolerability of hydromorphone extended release (ER) in patients with chronic low back pain (LBP) with or without a neuropathic component.Design: This was a post hoc analysis of data from a multicenter, double-blind, placebo-controlled clinical trial using a randomized withdrawal design, performed in patients with moderate to severe chronic LBP. Patients achieving stable doses of hydromorphone ER during a 2- to 4-week conversion and titration phase were randomized to continue treatment with hydromorphone ER or taper-down to placebo during a 12-week double-blind phase. The primary efficacy outcome was the mean change in 11-point Numeric Rating Scale (NRS) pain intensity score from randomization to the final visit of the double-blind phase. Tolerability was assessed by recording adverse events (AEs). Data were analyzed separately for patients with non-neuropathic and neuropathic LBP.Results: A total of 173 patients with non-neuropathic/nociceptive LBP and 94 with neuropathic LBP were randomized into the double-blind phase. During the conversion and titration phase, mean (SD) NRS scores decreased significantly from 6.5 (1.87) and 6.4 (1.99) at screening to 3.3 (0.98) and 3.2 (1.05), respectively. For both LBP subgroups, patients randomized to hydromorphone ER maintained this improvement over the double-blind treatment period, whereas those randomized to placebo reported significant increase in NRS scores. Across subgroups, the incidence of 1 or more AE was 54 percent to 57 percent in the conversion and titration phase and 47 percent to 55 percent in the double-blind phase.Conclusions: The results of this study indicate that hydromorphone ER is efficacious and generally well tolerated in the management of patients with non-neuropathic and neuropathic chronic LBP.

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Gao, Xiu Li, Wen Xu y Hua Li. "Interventions of Retarders on the Hydration Process of CaO Expansion Clinker". Applied Mechanics and Materials 584-586 (julio de 2014): 1573–76. http://dx.doi.org/10.4028/www.scientific.net/amm.584-586.1573.

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The volume deformation test, differential scanning calorimetry and chemical titration technique were used to experimentally research the interventions of retarders on the free autogenous volume deformation of cement paste doped with CaO expansion clinker at different ages systematically, as well as the hydration rate and hydration process of CaO expansion clinker. Two types of retarders were used as following: sodium gluconate and sodium citrate. The experimental results show that the two retarders can delay the hydration process of CaO expansion clinker, slow down its hydration rate both in pure water and cement paste. At the same time, the free autogenous volume deformation of cement paste was increased. In this sense, the use of retarders is favorable to improve the expansion efficiency of CaO expansion clinker.

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Fan, Yu, Yang Chen, Yueling Bai, Baoli An y Jiaqiang Xu. "A Novel 3D-Morphology Pyrene-Derived Conjugated Fluorescence Polymer for Picric Acid Detection". Nanomaterials 12, n.º 22 (17 de noviembre de 2022): 4034. http://dx.doi.org/10.3390/nano12224034.

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Aggregation-induced quenching (ACQ) is a hard problem in fluorescence material, leading to a poor utilization rate of fluorophores. In this work, 1,3,6,8-tetrakis(4-formylphenyl)pyrene (TFPPy) was synthesized and used as a precursor to build two kinds of fluorescence polymer. The TFFPy molecule with D2h symmetry can easily form polymers with C3 symmetry amines through the Schiff base reaction, making the resulting polymer a 3D amorphous material. Thus, ACQ of fluorophore can be reduced to minimum, making the most usage of the fluorescence of pyrene core. Fluorescence titration and DFT calculation can clearly prove this conclusion. The resulting CPs showed a highly sensitivity to picric acid, down to 3.43 ppm in solution, implying its potential in explosive detection.

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35

Dondi, Elisabetta, Els Pattyn, Georges Lutfalla, Xaveer Van Ostade, Gilles Uzé, Sandra Pellegrini y Jan Tavernier. "Down-modulation of Type 1 Interferon Responses by Receptor Cross-competition for a Shared Jak Kinase". Journal of Biological Chemistry 276, n.º 50 (15 de octubre de 2001): 47004–12. http://dx.doi.org/10.1074/jbc.m104316200.

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In contrast to the large number of class I and II cytokine receptors, only four Janus kinase (Jak) proteins are expressed in mammalian cells, implying the shared use of these kinases by many different receptor complexes. Consequently, if receptor numbers exceed the amount of available Jak, cross-interference patterns can be expected. We have engineered two model cellular systems expressing two different exogenous Tyk2-interacting receptors. A receptor chimera was generated wherein the extracellular part of the interferon type 1 receptor (Ifnar1) component of the interferon-α/β receptor is replaced by the equivalent domain of the erythropoietin receptor. Despite Tyk2 activation, erythropoietin treatment of cells expressing this erythropoietin receptor/Ifnar1 chimera did not evoke any detectable IFN-type response. However, a dose-dependent interference with signal transduction via the endogenous Ifnar complex was found for STAT1, STAT2, STAT3, Tyk2, and Jak1 activation, for gene induction, and for antiviral activity. In a similar approach, cells expressing the β1 chain of the interleukin-12 receptor showed a reduced transcriptional response to IFN-α as well as reduced STAT and kinase activation. In both model systems, titration of the Tyk2 kinase away from the Ifnar1 receptor chain accounts for the observed cross-interference.

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DJURDJEVIC-PAHL, Aleksandra, Chandralal HEWAGE y J. Paul G. MALTHOUSE. "13C-NMR study of the inhibition of δ-chymotrypsin by a tripeptide-glyoxal inhibitor". Biochemical Journal 362, n.º 2 (22 de febrero de 2002): 339–47. http://dx.doi.org/10.1042/bj3620339.

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A new inhibitor, Z-Ala-Pro-Phe-glyoxal (where Z is benzyloxycarbonyl),has been synthesized and shown to be a competitive inhibitor of δ-chymotrypsin, with a Ki of 25±8nM at pH7.0 and 25°C. Z-Ala-Pro-[1-13C]Phe-glyoxal and Z-Ala-Pro-[2-13C]Phe-glyoxal have been synthesized, and 13C-NMR has been used to determine how they interact with δ-chymotrypsin. Using Z-Ala-Pro-[2-13C]Phe-glyoxal we have detected a signal at 100.7p.p.m. which we assign to the tetrahedral adduct formed between the hydroxy group of Ser-195 and the 13C-enriched keto-carbon of the inhibitor. This signal is in a pH-dependent slow exchange with a signal at 107.6p.p.m. which depends on a pKa of ∼ 4.5, which we assign to oxyanion formation. Thus we are the first to detect an oxyanion pKa in a reversible chymotrypsin—inhibitor complex. A smaller titration shift of 100.7p.p.m. to 103.9p.p.m. with a pKa of ∼ 5.3 is also detected due to a rapid exchange process. This pKa is also detected with the Z-Ala-Pro-[1-13C]Phe-glyoxal inhibitor and gives a larger titration shift of 91.4p.p.m. to 97.3p.p.m., which we assign to the ionization of the hydrated aldehyde hydroxy groups of the enzyme-bound inhibitor. Protonation of the oxyanion in the oxyanion hole decreases the binding efficiency of the inhibitor. From this decrease in binding efficiency we estimate that oxyanion binding in the oxyanion hole reduces the oxyanion pKa by 1.3 pKa units. We calculate that the pKas of the oxyanions of the hemiketal and hydrated aldehyde moieties of the glyoxal inhibitor are both lowered by 6.4–6.9 pKa units on binding to chymotrypsin. Therefore we conclude that oxyanion binding in the oxyanion hole has only a minor role in decreasing the oxyanion pKa. We also investigate how the inhibitor breaks down at alkaline pH, and how it breaks down at neutral pH in the presence of chymotrypsin.

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Zhu, Y. T., E. J. Peterson, P. S. Baldonado, J. Y. Coulter, D. E. Peterson y F. M. Mueller. "Synthesis and crystal chemistry of the new compounds GdBa4Cu3O8.5+δ and DyBa4Cu3O8.5+δ". Journal of Materials Research 14, n.º 2 (febrero de 1999): 334–39. http://dx.doi.org/10.1557/jmr.1999.0049.

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Two new compounds, GdBa4Cu3O8.5+δ (Gd143) and DyBa4Cu3O8.5+δ (Dy143), were synthesized from precursors Gd2O3, Dy2O3, BaO2, and CuO at 1000 °C in an oxygen atmosphere. The oxygen stoichiometric value δ was found to be 0.68 for Gd143 and 0.6 for Dy143 by iodometric titration. Rietveld refinement of x-ray powder diffraction data showed that Gd143 belongs to the space group Pm3 while Dy143 belongs to the space group P23. The two space groups, Pm3 and P23, are very similar. Their main difference is that P23 does not have the inversion symmetry of Pm3. Both compounds have a cubic unit cell with a lattice parameter of 8.16528 ± 0.00006 Å for Gd143 and 8.10807 ± 0.00010 Å for Dy143. Superconducting quantum interference device (SQUID) measurement indicated that neither compound was superconductive down to 5 K.

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38

Tomson, Mason B., Amy T. Kan, Gongmin Fu y Lili Cong. "Measurement of Total Alkalinity and Carboxylic Acid and Their Relation to Scaling and Corrosion". SPE Journal 11, n.º 01 (1 de marzo de 2006): 103–10. http://dx.doi.org/10.2118/87449-pa.

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Summary Alkalinity is needed in many water-treatment calculations such as scale, corrosion, precipitation, and oxidation, yet the concept is often misunderstood. In natural waters, alkalinity often is not equal to bicarbonate concentration, because natural waters contain base-contributing anions that can significantly affect alkalinity. However, alkalinity is commonly assumed to be equal to the bicarbonate concentration in many scale- and corrosion-prediction algorithms. When other anions (e.g., carboxylates) are present, bicarbonate concentration in production tubing is not a conservative quantity; it varies with CO2 partial pressure, temperature, and carboxylate concentrations in a complicated manner up and down a well. Reliable methods to accurately measure true alkalinity are scarce, especially when multiple weak acids are present and the effects of TDS on electrode and color endpoint are significant. Oilfield brines contain aliphatic carboxylic acids of one to six carbons (e.g., acetate) up to 5000 mg/L. The highest concentrations of carboxylates tend to be in waters from reservoirs at temperatures of 80 to 100°C. In this paper, a new analytical procedure and computation routine to determine alkalinity and carboxylic acids simultaneously will be discussed. The procedure was recently debugged and simplified by the Rice U. Brine Chemistry Consortium (Rice BCC). The new titration method is based upon simultaneous analysis of the titration curve determined at fixed PCO2 and emphasizes the titration shape (profile) instead of the endpoint inflection as is done presently. A wide range of natural and synthetic waters has been tested. Excellent agreement was observed between the true and calculated carboxylic acid concentration with a correlation coefficient squared of 0.9986. Once the total alkalinity and acetic acid concentrations are determined, the theoretically correct bicarbonate concentration and/or pH at any given operation temperature or pressure can be calculated. The intricate interrelationship of total alkalinity, carboxylic acids, and pH on scale and corrosion will be discussed by using case studies.

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Biliuta, Gabriela, Raluca Ioana Baron y Sergiu Coseri. "Pullulan Oxidation in the Presence of Hydrogen Peroxide and N-Hydroxyphthalimide". Materials 15, n.º 17 (2 de septiembre de 2022): 6086. http://dx.doi.org/10.3390/ma15176086.

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The C-6 in the maltotriose unit of pullulan was oxidized in an alkaline medium (pH = 10), utilizing a green method that included hydrogen peroxide (H2O2) as an oxidant and N-hydroxyphthalimide (NHPI) as a catalyst for various reaction times. The structure of the resulting oxidized pullulans (PO) was carefully characterized by titration, intrinsic viscosity, FTIR, 13C-NMR, and zeta potential. The content of carboxyl groups in PO was dependent on reaction time and varied accordingly. Furthermore, a fast reaction rate was found in the first 2–3 h of the reaction, followed by a decreased rate in the subsequent hours. FTIR and 13C-NMR proved that the selective oxidation of the primary alcohol groups of pullulan was achieved. The oxidation also caused the glycoside linkages in the pullulan chain to break, and the viscosity of the pullulan itself went down.

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Wang, Yuanyuan, Zemao Gong, Han Fang, Dongming Zhi y Hu Tao. "The N-terminal 1–55 residues domain of pyruvate dehydrogenase from Escherichia coli assembles as a dimer in solution". Protein Engineering, Design and Selection 32, n.º 6 (junio de 2019): 271–76. http://dx.doi.org/10.1093/protein/gzz044.

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Abstract The pyruvate dehydrogenase complex (PDHc) from Escherichia coli is a large protein complex consisting of multiple copies of the pyruvate dehydrogenase (E1ec), dihydrolipoamide acetyltransferase (E2ec) and dihydrolipoamide dehydrogenase (E3ec). The N-terminal domain (NTD, residues 1–55) of E1ec plays a critical role in the interaction between E1ec and E2ec and the whole PDHc activity. Using circular dichroism, size-exclusion chromatography and dynamic light scattering spectroscopy, we show that the NTD of E1ec presents dimeric assembly under physiological condition. Pull-down and isothermal titration calorimetry binding assays revealed that the E2ec peripheral subunit-binding domain (PSBD) forms a very stable complex with the NTD, indicating the isolated NTD functionally interacts with PSBD and the truncated E1ec (E1ec∆NTD) does not interact with PSBD. These findings are important to understand the mechanism of PDHc and other thiamine-based multi-component enzymes.

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Serruto, Davide y Cesira L. Galeotti. "The signal peptide sequence of a lytic transglycosylase of Neisseria meningitidis is involved in regulation of gene expression". Microbiology 150, n.º 5 (1 de mayo de 2004): 1427–37. http://dx.doi.org/10.1099/mic.0.26780-0.

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The 60 nucleotides encoding the signal peptide of the Neisseria meningitidis membrane-bound lytic transglycosylase (MltA) homologue GNA33 were found to exert a negative regulatory effect on expression of GNA33 from either a T7- or a Plac-driven system in Escherichia coli. Down-regulation was observed to occur at the transcriptional/post-transcriptional level and could possibly be ascribed to the formation of a stem–loop secondary structure within the signal peptide sequence. Slowing down the transcription rate through inhibition/titration of the RNA polymerase resulted in a considerable increase in mRNA accumulation, suggesting that a better coupling of translation to transcription would impede the formation of the putative secondary structure. Screening of synonymous mutations in the signal peptide sequence that showed high-level expression of an in-frame fusion to a reporter resulted in the isolation of several deletion mutants lacking most of the sequence participating in the putative secondary structure. Interestingly, the increase in the steady-state mRNA level observed in deletion mutants was higher, reaching a 300-fold increment, than that found in substitution mutants. Our results support the hypothesis that the rate of transcription controls the formation of a secondary structure in the region of the GNA33 transcript corresponding to the signal peptide sequence and this, when formed, negatively regulates expression.

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Seliger, Stephen L. "Hyperkalemia in patients with chronic renal failure". Nephrology Dialysis Transplantation 34, Supplement_3 (1 de diciembre de 2019): iii12—iii18. http://dx.doi.org/10.1093/ndt/gfz231.

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Abstract Although hyperkalemia is much more common in patients with chronic kidney disease (CKD), the reported frequency of hyperkalemia varies markedly across studies, primarily due to differences in the ascertainment of hyperkalemia and the severity of CKD. Major risk factors for hyperkalemia among CKD patients include lower estimated glomerular filtration rate (eGFR), use of renin–angiotensin–aldosterone system inhibitors (RAASis), diabetes, older age and male gender. The use of two drugs to inhibit RAAS in diabetic CKD markedly increases the risk of hyperkalemia, as demonstrated in large multicenter clinical trials. Hyperkalemia has consistently been associated with an increased risk of adverse events compared with normokalemia, including all-cause mortality and cardiovascular morbidity and mortality. This risk is not explained by differences in comorbidity or estimated GFR, nor concomitant metabolic abnormalities such as acidosis among those with hyperkalemia. Sodium polystyrene sulfonate has been used commonly for decades to treat hyperkalemia in CKD patients, but without any high-quality clinical data to support its efficacy and with an increased risk of rare but serious colonic complications. The newer oral potassium-binding agents, patiromer and sodium zirconium cyclosilicate, have been shown to be effective and safe for the non-emergent treatment of hyperkalemia in CKD patients, including patients treated with RAASis. Although the long-term use of these medications may permit continuation of RAASis in CKD patients with hyperkalemia, the overall impact of this approach (as compared with down-titration of RAASis and/or up-titration of diuretics) on long-term morbidity, mortality and quality of life remains uncertain.

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HEIKMAN, P., A. TUUNAINEN y K. KUOPPASALMI. "Value of the initial stimulus dose in right unilateral and bifrontal electroconvulsive therapy". Psychological Medicine 29, n.º 6 (noviembre de 1999): 1417–23. http://dx.doi.org/10.1017/s0033291799001245.

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Background. The outcome of electroconvulsive therapy (ECT) is affected by the placement and dose of the stimulus. In general, the ECT dose can be selected either by the dose-titration method (on which the measured seizure threshold level is based), or the method of predetermined dose (e.g. the age-based dosing and the fixed high dose method).Methods. Seizure thresholds were measured in 50 patients with right unilateral (RUL) and in 30 patients with experimental bifrontal (BF) ECT stimulus. The ECT dose (mC) of the age-based dosing was calculated by multiplying the age (years) by 5·0 (age method) or 2·5 (half-age method). The fixed high dose was set to 378 mC.Results. The seizure thresholds had only a moderate correlation with the age of the patients. The methods based on the predetermined dose would have led us to give patients with the lowest seizure thresholds in the RUL ECT group very high stimulus doses, up to 12 (age method) or 15 (fixed high dose method) times the individual seizure threshold. In contrast, the RUL ECT patients with the highest seizure thresholds would have received low stimulus doses down to 1·5 times (half-age method) the initial seizure threshold. In the BF ECT group the-age based dose would have been similarly dependent on the initial seizure threshold level.Conclusion. The use of the dose-titration method is recommended, because it is the only method that allows for the individual selection of ECT stimulus dose relative to the seizure threshold.

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Power, Adam, Asha Parekh, Neil Parry y Laura J. Moore. "Cushioned on the way up, controlled on the way down during resuscitative endovascular balloon occlusion of the aorta (REBOA): investigating a novel compliant balloon design for optimizing safe overinflation combined with partial REBOA ability". Trauma Surgery & Acute Care Open 7, n.º 1 (julio de 2022): e000948. http://dx.doi.org/10.1136/tsaco-2022-000948.

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BackgroundThere are a variety of devices capable of performing resuscitative endovascular balloon occlusion of the aorta (REBOA), with most containing compliant balloon material. While compliant material is ideal for balloon inflation due to its “cushioning” effect, it can be problematic to “control” during deflation. The COBRA-OS (Control Of Bleeding, Resuscitation, Arterial Occlusion System) was designed to optimize inflation and deflation of its compliant balloon and was tested in vitro and in vivo with respect to its overinflation and partial REBOA abilities.MethodsFor overinflation, the COBRA-OS was inflated in three differently sized inner diameter (ID) vinyl tubes until balloon rupture. It was then overinflated in six harvested swine aortas and in all three REBOA zones of three anesthetized swine. For partial REBOA, the COBRA-OS underwent incremental deflation in a pulsatile benchtop aortic model and in zone 1 of three anesthetized swine.ResultsFor overinflation, compared with the known aortic rupture threshold of 4 atm, the COBRA-OS exceeded this value in only the smallest of the vinyl tubes: 8 mm ID tube, 6.5 atm; 9.5 mm ID tube, 3.5 atm; 13 mm ID tube, 1.5 atm. It also demonstrated greater than 500% overinflation ability without aortic damage in vitro and caused no aortic damage when inflated to maximum inflation volume in vivo. For partial REBOA, the COBRA-OS was able to provide a titration window of between 3 mL and 4 mL in both the pulsatile vascular model (3.4±0.12 mL) and anesthetized swine (3.8±0.35 mL).DiscussionThe COBRA-OS demonstrated the ability to have a cushioning effect during inflation combined with titration control on deflation in vitro and in vivo. This study suggests that despite its balloon compliance, both safe overinflation and partial REBOA can be successfully achieved with the COBRA-OS.Level of evidenceBasic science.

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Verhestraeten, Caroline, Gijs Weijers, Daphne Debleu, Agnieszka Ciarka, Marc Goethals, Steven Droogmans y Michael Maris. "Diagnosis, treatment, and follow-up of heart failure patients by general practitioners: A Delphi consensus statement". PLOS ONE 15, n.º 12 (31 de diciembre de 2020): e0244485. http://dx.doi.org/10.1371/journal.pone.0244485.

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Aims Creation of an algorithm that includes the most important parameters (history, clinical parameters, and anamnesis) that can be linked to heart failure, helping general practitioners in recognizing heart failure in an early stage and in a better follow-up of the patients. Methods and results The algorithm was created using a consensus-based Delphi panel technique with fifteen general practitioners and seven cardiologists from Belgium. The method comprises three iterations with general statements on diagnosis, referral and treatment, and follow-up. Consensus was obtained for the majority of statements related to diagnosis, referral, and follow-up, whereas a lack of consensus was seen for treatment statements. Based on the statements with good and perfect consensus, an algorithm for general practitioners was assembled, helping them in diagnoses and follow-up of heart failure patients. The diagnosis should be based on three essential pillars, i.e. medical history, anamnesis and clinical examination. In case of suspected heart failure, blood analysis, including the measurement of NT-proBNP levels, can already be performed by the general practitioner followed by referral to the cardiologist who is then responsible for proper diagnosis and initiation of treatment. Afterwards, a multidisciplinary health care process between the cardiologist and the general practitioner is crucial with an important role for the general practitioner who has a key role in the up-titration of heart failure medication, down-titration of the dose of diuretics and to assure drug compliance. Conclusions Based on the consensus levels of statements in a Delphi panel setting, an algorithm is created to help general practitioners in the diagnosis and follow-up of heart failure patients.

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Kane, Peter y Tim Fitzpatrick. "Studies in Adapting the Modified Comprehensive Method for Fertilizer Nitrogen to Block Digestion/Steam Distillation". Journal of AOAC INTERNATIONAL 73, n.º 1 (1 de enero de 1990): 80–82. http://dx.doi.org/10.1093/jaoac/73.1.80.

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Abstract A high temperature heating block has been successfully used as an alternative apparatus to traditional Kjeldahl digestion for methods involving various organic nitrogen samples. But the block has not been successfully used for a fertilizer nitrogen methodology. This paper describes an attempt to adapt the AOAC modified comprehensive method for fertilizer nitrogen to the block, followed by steam distillation and titration. A wide variety of reduction conditions were found satisfactory to reduce the N03- nitrogen from KN03. More rigorous digestion parameters, a 450°C block temperature, higher than normal salt/acid ratios, and air condensers to contain the digestion acid were found necessary to achieve full nitrogen recovery from lysine*HCI. The remaining hindrance to a successful fertilizer nitrogen block methodology is that a chromium NH4 + complex found in the digests requires about 30 min to be broken down during the steam distillation step. This is not practical for routine analysis.

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47

McDonald, Louise, Gavin Baker y Olga Kerr. "Scalp ulceration: a rare manifestation of giant cell arteritis". BMJ Case Reports 12, n.º 11 (noviembre de 2019): e230795. http://dx.doi.org/10.1136/bcr-2019-230795.

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An 81-year-old woman presented with an enlarging, tender ulcer on her scalp over an 8-week period, attributing it to a prior graze with garden shears. C-reactive protein and erythrocyte sedimentation rate were elevated at 87.7 mg/L and 112 mm/hour, respectively. Incisional biopsies demonstrated ulceration and full thickness necrosis with no evidence of malignancy. Vasculitis was suggested as a likely cause of such extensive necrosis and subsequent temporal artery biopsy findings were consistent with giant cell arteritis. The patient was initially treated with high-dose oral prednisolone and achieved complete healing of the scalp necrosis within 12 months, with a gradual down-titration of steroid therapy thereafter. Scalp necrosis is a rare, potentially life-threatening complication of giant cell arteritis. This case highlights the importance of considering scalp necrosis as a manifestation of giant cell arteritis when assessing scalp ulceration. Prompt diagnosis and treatment can prevent significant morbidity and potential mortality.

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48

Reich, K., E. Simpson, A. Wollenberg, R. Bissonnette, M. Abe, T. Cardillo, J. Janes, L. Sun, S. Chen y J. Silverberg. "041 Efficacy with continuous dosing, down-titration, or treatment withdrawal after successful treatment with baricitinib in patients with moderate-to-severe atopic dermatitis". Journal of Investigative Dermatology 141, n.º 10 (octubre de 2021): S155. http://dx.doi.org/10.1016/j.jid.2021.08.043.

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Lee, Yonggu, Jinho Shin y Wook Bum Pyun. "PS-P15-2: CHANGES IN HOME BLOOD PRESSURE VARIABILITY DURING DOWN-TITRATION OF ANTIHYPERTENSIVE DRUGS IN PATIENT WITH SYSTOLIC HOME BLOOD PRESSURE BELOW 120MMHG". Journal of Hypertension 41, Suppl 1 (enero de 2023): e502. http://dx.doi.org/10.1097/01.hjh.0000918048.54136.39.

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50

Campbell, Patricia, Paul McKeveney, Kay Donegan, Charlie Ataliotis, Carol Patton y Robert Mullan. "Practical guidance for the use of potassium binders in the management of hyperkalaemia in patients with heart failure and/or chronic kidney disease". British Journal of Hospital Medicine 82, n.º 4 (2 de abril de 2021): 1–11. http://dx.doi.org/10.12968/hmed.2021.0215.

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Given the critical physiological role of potassium, it is understandable that the development of severe hyperkalaemia requires effective management to reduce its effects, which include muscle weakness, paralysis and cardiac arrhythmias. Hyperkalaemia most often results from the failure of renal adaptation to potassium imbalance. Patients who are most susceptible to the development of hyperkalaemia include those with chronic kidney disease and those with heart failure. These patients are often treated with renin–angiotensin–aldosterone system (RAAS) inhibitors, such as angiotensin-converting enzyme inhibitors and angiotensin II-receptor blockers, but the development of hyperkalaemia can require down-titration or cessation of RAAS inhibitors. This presents a significant challenge to nephrologists, cardiologists and healthcare professionals treating these patients as this can prevent them from receiving maximum guideline-directed RAAS inhibitor therapy. Panellists in this roundtable discussion shared their clinical experiences of using potassium binders to manage hyperkalaemia in patients with chronic kidney disease and patients with heart failure (illustrated with case studies) in Northern Ireland and considered recommendations for the implementation and maintenance of chronic potassium-lowering treatment.

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