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Background Plasma amino acid analysis is key to the diagnosis and monitoring of inherited disorders of amino acid synthesis, catabolism and transport. Ion exchange chromatography (IEC) is widely accepted as the gold standard metho...
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Background Plasma amino acid analysis is key to the diagnosis and monitoring of inherited disorders of amino acid synthesis, catabolism and transport. Ion exchange chromatography (IEC) is widely accepted as the gold standard method of analysis, but with the introduction of liquid chromatography tandem mass spectrometry (LC-MS/MS) and liquid chromatography mass spectrometry (LC-MS) methods, this should now be questioned. Methods The analytical performance of three commercially available reagent kits, Waters AccQ Tag (TM) ULTRA LC-MS, SpOtOn Amino Acids LC-MS/MS and Chromsystems MassChrom (R) Amino Acid Analysis LC-MS/MS, were evaluated and compared with Biochrom Physiological Amino Acids ion exchange chromatography. Correlation with IEC was assessed by Passing-Bablok regression, concordance correlation coefficients (CCC) and Bland-Altman analysis for 21 common amino acids. Calculation of the total error from imprecision and bias was also used to benchmark performance. Results The MassChrom (R) and SpOtOn kits demonstrated acceptable inter-batch imprecision (CV 0.95) with Biochrom IEC was demonstrated for 10/21 analytes in both the MassChrom (R) and SpOtOn kits and 6/21 in the AccQ Tag (TM) ULTRA kit. Conclusions The LC-MS assay demonstrated variable analytical performance and correlated poorly with ion exchange chromatography. Both LC-MS/MS assays demonstrated comparable analytical performance and reasonable correlation with ion exchange chromatography. They also confer practical advantages which cannot be realized by ion exchange chromatography, superior specificity and significantly faster analysis time, suggesting that ion exchange chromatography should no longer be described as the gold standard method for plasma amino acid analysis.
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Small extracellular vesicles (SEVs) offer a promising strategy for tissue regeneration, yet their short lifetime at the injured tissue limits their efficacy. Here, we show that kinetics of SEV delivery impacts tissue regeneration ...
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Small extracellular vesicles (SEVs) offer a promising strategy for tissue regeneration, yet their short lifetime at the injured tissue limits their efficacy. Here, we show that kinetics of SEV delivery impacts tissue regeneration at tissue, cellular, and molecular levels. We show that multiple carefully timed applications of SEVs had superior regeneration than a single dose of the same total concentration of SEVs. Importantly, diabetic and non diabetic wounds treated with a single time point dose of an injectable light-triggerable hydrogel containing SEVs demonstrated a robust increase in closure kinetics relative to wounds treated with a single or multiple doses of SEVs or platelet-derived growth factor BB, an FDA-approved wound regenerative therapy. The pro-healing activity of released SEVs was mediated at the tissue/cell level by an increase in skin neovascularization and re-epithelization and at the molecular level by an alteration in the expression of 7 miRNAs at different times during wound healing. This includes an alteration of has-miR-150-5p, identified here to be important for skin regeneration.
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Despite the known protective cardiovascular effect of aspirin, former studies identified its prior exposure to an acute coronary syndrome (ACS) as an independent risk factor for adverse events. However, those studies did not refle...
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Despite the known protective cardiovascular effect of aspirin, former studies identified its prior exposure to an acute coronary syndrome (ACS) as an independent risk factor for adverse events. However, those studies did not reflect contemporary approaches. In the current study, we determine whether patients exposed to aspirin before an ACS have a worse cardiovascular risk profile and if it predicts higher risk of recurrent cardiovascular events or mortality. A cohort of patients enrolled in a national registry of ACS was analyzed according to prior exposure to aspirin. A propensity score standardized patients according to baseline comorbidities. Multivariable COX regression analysis was performed in unmatched and matched populations for a primary endpoint (composite of all-cause mortality and/or cardiovascular rehospitalization) and two secondary endpoints (all-cause mortality and cardiovascular rehospitalization, separately) at 1-year follow-up. Among 5533 ACS patients, 1763 were previously exposed to aspirin. They were older and had more comorbidities; contemporary approaches, both coronary angiography and percutaneous coronary angioplasty were less likely to be performed. Before matching the population, prior exposure to aspirin was an independent predictor of primary composite endpoint (p = 0.002) and cardiovascular rehospitalization as the secondary endpoint (p = 0.001). There were no statistically significant differences between both groups in the multivariable model for the primary or secondary endpoints after matching. Previous exposure to aspirin identified ACS patients with worse baseline characteristics, establishing its role as a cardiovascular risk marker. However, our data do not support including aspirin pretreatment in risk stratification scores as an adverse prognostic variable.
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The toxicity induced in non-target organisms by pharmaceutical drugs has been the focus of several studies. In the aquatic environment, most of the studies have been devoted to fish and bivalves, while little is known on the impac...
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The toxicity induced in non-target organisms by pharmaceutical drugs has been the focus of several studies. In the aquatic environment, most of the studies have been devoted to fish and bivalves, while little is known on the impacts induced in polychaetes. The present study evaluated the impacts of carbamazepine and caffeine on the regenerative capacity of Diopatra neapolitana, a polychaete species with high ecological and economic relevance. Under laboratory controlled conditions polychaetes were exposed, during 28 days, to carbamazepine (Ctl-0.0; 0.3; 3.0; 6.0; 9.0 mu g/L) and caffeine (Ctl-0.0; 0.5; 3.0; 18.0 mu g/L). During the experiment, at days 11, 18, 25, 32, 39 and 46 after amputation, for each specimen, the percentage of the body width regenerated was determined and the number of new segments was counted. The regenerative capacity was assessed considering the number of days needed to achieve full regeneration and the total number of new segments. The obtained results revealed that with the increase of drugs concentrations organisms regenerated less new segments and took longer to completely regenerate. (C) 2015 Elsevier Ltd. All rights reserved.
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Introduction: The majority of patients with ankle injuries undergo radiological examinations of the foot, ankle or both. The objective of this study was in the first place to validate the Ottawa Ankle Rules (OARs) for the populati...
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Introduction: The majority of patients with ankle injuries undergo radiological examinations of the foot, ankle or both. The objective of this study was in the first place to validate the Ottawa Ankle Rules (OARs) for the population of our centre. Secondly, an attempt was made to identify parameters that contribute to improve the specificity of the method, with a view to reduce the need for patients to be exposed to radiation as well as optimizing the expenses of the Emergency Ward (EW).
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PMM2-CDG is the most common congenital disorder of glycosylation (CDG) accounting for almost 65% of known CDG cases affecting N-glycosylation. Abnormalities in N-glycosylation could have a negative impact on many endocrine axes. T...
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PMM2-CDG is the most common congenital disorder of glycosylation (CDG) accounting for almost 65% of known CDG cases affecting N-glycosylation. Abnormalities in N-glycosylation could have a negative impact on many endocrine axes. There is very little known on the effect of impaired N-glycosylation on the hypothalamic pituitary-adrenal axis function and whether CDG patients are at risk of secondary adrenal insufficiency and decreased adrenal cortisol production. Cortisol and ACTH concentrations were simultaneously measured between 7:44 am to 1 pm in forty-three subjects (20 female, median age 12.8 years, range 0.1 to 48.6 years) participating in an ongoing international, multicenter Natural History study for PMM2-CDG (ClinicalTrials.gov Identifier: NCT03173300). Of the 43 subjects, 11 (25.6%) had cortisol below 5 Ng/dl and low to normal ACTH levels, suggestive of secondary adrenal insufficiency. Two of the 11 subjects have confirmed central adrenal insufficiency and are on hydrocortisone replacement and/ or stress dosing during illness; 3 had normal and 1 had subnormal cortisol response to ACTH low-dose stimulation test but has not yet been started on therapy; the remaining 5 have upcoming stimulation testing planned. Our findings suggest that patients with PMM2-CDG may be at risk for adrenal insufficiency. Monitoring of morning cortisol and ACTH levels should be part of the standard care in patients with PMM2-CDG. (c) 2021 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license (http:// creativecommons.org/licenses/by-nc-nd/4.0/).
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PMM2-CDG is the most common congenital disorder of glycosylation (CDG) accounting for almost 65% of known CDG cases affecting N-glycosylation. Abnormalities in N-glycosylation could have a negative impact on many endocrine axes. T...
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PMM2-CDG is the most common congenital disorder of glycosylation (CDG) accounting for almost 65% of known CDG cases affecting N-glycosylation. Abnormalities in N-glycosylation could have a negative impact on many endocrine axes. There is very little known on the effect of impaired N-glycosylation on the hypothalamic pituitary-adrenal axis function and whether CDG patients are at risk of secondary adrenal insufficiency and decreased adrenal cortisol production. Cortisol and ACTH concentrations were simultaneously measured between 7:44 am to 1 pm in forty-three subjects (20 female, median age 12.8 years, range 0.1 to 48.6 years) participating in an ongoing international, multicenter Natural History study for PMM2-CDG (ClinicalTrials.gov Identifier: NCT03173300). Of the 43 subjects, 11 (25.6%) had cortisol below 5 Ng/dl and low to normal ACTH levels, suggestive of secondary adrenal insufficiency. Two of the 11 subjects have confirmed central adrenal insufficiency and are on hydrocortisone replacement and/ or stress dosing during illness; 3 had normal and 1 had subnormal cortisol response to ACTH low-dose stimulation test but has not yet been started on therapy; the remaining 5 have upcoming stimulation testing planned. Our findings suggest that patients with PMM2-CDG may be at risk for adrenal insufficiency. Monitoring of morning cortisol and ACTH levels should be part of the standard care in patients with PMM2-CDG. (c) 2021 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license (http:// creativecommons.org/licenses/by-nc-nd/4.0/).
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We report a clinical case of a 40-year-old male with surgically corrected congenital heart disease (CHD) 10 years earlier: closure of ostium primum, mitral annuloplasty, and aortic valve and root surgery. The patient was admitted ...
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We report a clinical case of a 40-year-old male with surgically corrected congenital heart disease (CHD) 10 years earlier: closure of ostium primum, mitral annuloplasty, and aortic valve and root surgery. The patient was admitted with acute heart failure. Transesophageal echocardiography (TEE) revealed a dysmorphic and severely incompetent aortic valve, a partial tear of the mitral valve cleft repair and annuloplasty ring dehiscence. A true left ventricular-to-right atrial shunt confirmed a direct Gerbode defect. The authors aim to discuss the diagnostic challenge of adult CHD, namely the key role of TEE on septal defects and valve regurgitations description.
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