In silico synchronization reveals regulators of nuclear ruptures in lamin A/C deficient model cells

The nuclear lamina is a critical regulator of nuclear structure and function. Nuclei from laminopathy patient cells experience repetitive disruptions of the nuclear envelope, causing transient intermingling of nuclear and cytoplasmic components. The exact causes and consequences of these events are not fully understood, but their stochastic occurrence complicates in-depth analyses. To resolve this, we have established a method that enables quantitative investigation of spontaneous nuclear ruptures, based on co-expression of a rmly bound nuclear reference marker and a uorescent protein that shuttles between the nucleus and cytoplasm during ruptures. Minimally invasive imaging of both reporters, combined with automated tracking and in silico synchronization of individual rupture events, allowed extracting information on rupture frequency and recovery kinetics. Using this approach, we found that rupture frequency correlates inversely with lamin A/C levels, and can be reduced in genome- edited LMNA knockout cells by blocking actomyosin contractility or inhibiting the acetyl-transferase protein NAT10. Nuclear signal recovery followed a kinetic that is co-determined by the severity of the rupture event, and could be prolonged by knockdown of the ESCRT-III complex component CHMP4B. In conclusion, our approach reveals regulators of nuclear rupture induction and repair, which may have critical roles in disease development

Evaluation of a novel skin care product for the management of chemotherapy-related dermatologic toxicities: A quasi-experimental study

Purpose: Evaluate the efficacy of a novel skincare product for the management of chemotherapy-related dermatological toxicities. Methods: A monocentric, prospective, interventional, open-label, pretest-posttest, single-group study with cancer patients receiving chemotherapy (n = 100) was set up. All enrolled patients applied the emollient daily to their face and body for three weeks. The severity of the skin reactions was evaluated by a researcher using the Common Terminology Criteria for Adverse Events (CTCAE) v5.0 at baseline and end of the trial. Patient-reported outcomes (PROs) included the frequency and severity of skin symptoms (Numerical rating scale, NRS), quality of life (QoL; Skindex-16 and Dermatology Life Quality Index), Patient Benefit Index (PBI), and treatment satisfaction. PROs were collected at baseline, weekly, and at the end of the trial. Results: According to the CTCAE and NRS, the novel emollient significantly improved the severity and frequency of xerosis and pruritus (Ps <= .001). A significant reduction in the NRS score for frequency of erythema was measured (p < .001). The frequency and severity of burning and pain did not change. Regarding the patients' QoL, no beneficial effect of the skin care product was measurable. 44% of the patients experienced at least one patient-relevant treatment benefit. 87% of the patients were satisfied with the emollient and would recommend it. Conclusions: This study shows that the novel emollient significantly reduced chemotherapy-induced skin toxicity, more specifically xerosis and pruritus without hampering patient's QoL. Future research is needed to make definite conclusions using a study design including a control group and a long-term follow-up

Commutability of proficiency testing material containing amitriptyline and nortriptyline:A study within the framework of the Dutch Calibration 2.000 project

BACKGROUND: External quality assessment schemes (EQAS) can provide important information regarding accuracy and comparability of different measurement methods if the sample matrices are composed of commutable material. The aim of this study was to assess the commutability of different matrices for the material used in an EQAS for amitriptyline and nortriptyline. METHODS: Proficiency testing material (PTM) and patient samples containing amitriptyline and nortriptyline were prepared, collected, pooled, and distributed to participating laboratories for analysis. Low, medium and high concentrations of both drugs in liquid pooled human, lyophilized human and lyophilized bovine serum were tested in this study. The measurement deviation of the PTM results to the patient serum regression line were normalized by dividing trough the average within-laboratory SD (SDwl) derived from the results reported in the official EQAS, resulting in a relative residual. The commutability decision limit was set at 3 SDwl. RESULTS: With 10 laboratories participating in this study, 45 laboratory couples were formed. All matrix types delivered several relative residuals outside the commutability decision limit. The number and the magnitude of relative residuals for both drugs were lower for liquid human sera as compared to lyophilized human and bovine sera. CONCLUSIONS: The PTM used for amitriptyline and nortriptyline is preferably prepared with human serum, although not all relative residuals are within the commutability decision limit

Commutability of proficiency testing material containing amitriptyline and nortriptyline: A study within the framework of the Dutch Calibration 2.000 project

Background: External quality assessment schemes (EQAS) can provide important information regarding accuracy and comparability of different measurement methods if the sample matrices are composed of commutable material. The aim of this study was to assess the commutability of different matrices for the material used in an EQAS for amitriptyline and nortriptyline. Methods: Proficiency testing material (PTM) and patient samples containing amitriptyline and nortriptyline were prepared, collected, pooled, and distributed to participating laboratories for analysis. Low, medium and high concentrations of both drugs in liquid pooled human, lyophilized human and lyophilized bovine serum were tested in this study. The measurement deviation of the PTM results to the patient serum regression line were normalized by dividing trough the average within-laboratory SD (SDwl) derived from the results reported in the official EQAS, resulting in a relative residual. The commutability decision limit was set at 3 SDwl. Results: With 10 laboratories participating in this study, 45 laboratory couples were formed. All matrix types delivered several relative residuals outside the commutability decision limit. The number and the magnitude of relative residuals for both drugs were lower for liquid human sera as compared to lyophilized human and bovine sera. Conclusions: The PTM used for amitriptyline and nortriptyline is preferably prepared with human serum, although not all relative residuals are within the commutability decision limit

A Multilaboratory Commutability Evaluation of Proficiency Testing Material for Carbamazepine and Valproic Acid:A Study Within the Framework of the Dutch Calibration 2000 Project

Background: Medical laboratories are required to participate in interlaboratory comparisons of the analyses they perform. The materials used in these comparisons need to be of sufficient quality so that the comparison provides a picture of the performances. One of the main characteristics of the testing material is commutability, which is the ability of a material to yield the same numerical relationships between results of measurements as those relationships obtained when the same procedures are applied to patient samples. The aim of this study was to assess the commutability of 3 different matrices for the preparation of proficiency testing material (PTM) for the analysis of carbamazepine and valproic acid. Methods: Patient samples and PTM containing various concentrations of carbamazepine and valproic acid were collected, prepared, and shipped to different laboratories for analysis. Reported results for patient samples from each laboratory were plotted against results for patient samples of each of the other laboratories, and the corresponding regression line was calculated. The distance of results from PTM to the regression line is a measure for commutability. The distance is expressed as a multiple of the SDwl (average within-laboratory SD as calculated from external quality assessment scheme results) and referred to as relative residual. A commutability decision limit of 2 SDwl was set. Results: For carbamazepine and valproic acid, a total of 78 and 105 laboratory couples respectively could be formed. The number of relative residuals for liquid human serum outside the commutability decision limit was 1, 4, and 0 for low, medium, and high concentrations of carbamazepine, respectively and 3, 1, and 0 for low, medium, and high concentrations of valproic acid, respectively. In both liquid and lyophilized bovine sera, the number of relative residuals outside the commutability decision limit was between 2 and 15 and between 6 and 21 for carbamazepine and valproic acid, respectively. Conclusions: Although not all results for PTM with carbamazepine and valproic acid are within the commutability decision limits, a preference for human serum can be seen

Commutability of proficiency testing material containing tobramycin:a study within the framework of the Dutch Calibration 2.000 project

Background: Results from external quality assessment schemes (EQASs) can provide information about accuracy and comparability of different measurement methods, provided that the material used in these schemes behave identical to patient samples among the different methods, a characteristic also known as commutability. The aim of this study was to assess the commutability of different matrices for the material used in an EQAS for tobramycin. Methods: Proficiency testing material (PTM) and patient samples containing tobramycin were prepared, collected, pooled, and distributed to participating laboratories for analysis. Low, medium, and high tobramycin concentrations in liquid human, liquid bovine and lyophilized bovine serum were tested in this study. The patient serum results of every laboratory were plotted against each of the other laboratories, and the distances of the PTM results to the patient serum regression line were calculated. For comparison, these distances were divided by the average within-laboratory standard deviation (SDwl) of the results reported in the official EQAS for tobramycin, resulting in a relative residual. The commutability decision limit was set at 3 SDwl. Results: With 10 laboratories participating in this study, 45 laboratory couples were formed. For human serum, only one relative residual for high concentrations of tobramycin was found outside the commutability decision limit. For liquid and lyophilized bovine sera, the number of relative residuals outside the decision limit was between 15 and 18 for low, medium, and high tobramycin concentrations. Conclusions: The PTM used for tobramycin is preferably prepared with human serum

Monitoring des animaux vivants : exemple d’un échantillonnage pour la détection des PCBs et des dioxines chez les bovins de boucherie en Belgique

peer reviewedIn February 1999, a poisoning episode broke out in several industrial poultry farms in Belgium. The source of this contamination was found to be a stock of recycled fat that had been delivered by a firm to several compound feed producers, between 19 and 31 January 1999. A very good correlation was observed between dioxins (PCDFs and PCDDs) and PCBs. Consequently a contamination mainly by PCBs was hypothesized. This finding made it possible to detect contaminated animals and animal products by dosage of the PCBs, more specifically by the 7 congeners with numbers 28, 52, 101, 118, 138, 153 and 180. The advantages of the dosage of PCBs compared to dioxins were its rapid test protocol and the fact that a larger number of laboratories could participate. In the cattle sector, 409 herds (0,81 p. cent) were submitted to the risk of feed contamination. The methodology used to detect a PCBs/dioxins contamination in the Belgian cattle population that was not submitted to the risk, is presented. This population is directly or indirectly destined for human consumption. It consisted in the systematic sampling of all calve fattening stations and all lots of exported bovines, and in the random sampling of slaughter cattle. This methodology is compared to the approach described in directive 96/23/CE.La contamination par les polychlorobiphényls PCBs/dioxines de la chaîne alimentaire en Belgique s'est révélée en février 1999 dans des élevages industriels de volailles. Fin avril 1999, suite à l'enquête alimentaire, il s'est avéré que la source de contamination était un stock de graisses recyclées ayant été livrées par une firme à plusieurs fabricants d'aliments composés pour animaux, entre le 15 et le 31 janvier 1999. Une relation étroite a été mise en évidence entre les quantités de dioxines (PCDFs et PCDDs) et celles des PCBs, étayant ainsi l'hypothèse d'une contamination principale par les PCBs. Cette constatation a permis de baser le dépistage des animaux et des produits animaux susceptibles d'avoir été contaminés sur le dosage des 7 congénères PCBs numéros 28, 52, 101, 118, 138, 153 et 180. Ce dosage offrait l'avantage d'être rapide et réalisable par un plus grand nombre de laboratoires contrairement à celui des dioxines. En ce qui concerne le secteur des bovins, 409 troupeaux ont été soumis au risque alimentaire (0,81 p. cent du total des troupeaux belges). Ces troupeaux ont été placés sous saisie conservatoire et la levée de celle-ci a été effectuée soit sur base des résultats d'enquêtes épidémiologiques et alimentaires, soit sur base des résultats d'analyses PCBs/dioxines effectuées sur un échantillonnage représentatif des troupeaux bovins concernés ou soit sur base de la mise à mort et l’incinération de tous les bovins des 6 troupeaux pour lesquels des résultats d’analyses PCBs/dioxines étaient supérieurs aux normes fixées (PCBs : ≤ 100 ng/g MG dans le lait, ≤ 200 ng/g MG dans les graisses corporelles ; dioxines ≤ 5 pg TEQ/g MG) [Anonyme, 1999]. L'approche méthodologique qui a été utilisée pour détecter une contamination par les PCBs/dioxines au sein de la population des bovins belges non soumise au risque alimentaire est présentée. Cette approche est basée sur l'échantillonnage systématique de toutes les stations d'engraissement de veaux, l'échantillonnage systématique des lots de bovins destinés à l'exportation et l'échantillonnage aléatoire des bovins abattus en Belgique durant une semaine. Cette approche est comparée à celle préconisée par la directive 96/23/CE du Conseil