Age Is the Only Predictor of Poor Bowel Preparation in the Hospitalized Patient

We examine the impact of key variables on the likelihood of inpatient poor bowel preparation for colonoscopy. Records of inpatients that underwent colonoscopy at our institution between January 2010 and December 2011 were retrospectively extracted. Univariable and multivariable logistic regression models were fitted to assess the effect of clinical variables on the odds of poor preparation. Tested predictors included age; gender; use of narcotics; heavy medication burden; comorbidities; history of previous abdominal surgery; neurological disorder; product used for bowel preparation, whether or not the bowel regimen was given as split or standard dose; and time of endoscopy. Overall, 244 patients were assessed including 83 (34.0%, 95% CI: 28.1–39.9%) with poor bowel preparation. Cecal intubation was achieved in 81.1% of patients (95% CI: 76.2–86.0%). When stratified by quality of bowel preparation, cecal intubation was achieved in only 65.9% (95% CI: 60.0–71.9%) of patients with poor bowel preparation and 89.9% (95% CI: 86.1–93.7%) of patient with good bowel preparation. In multivariate logistic regression analysis, only advancing age was an independent predictor of poor bowel preparation (OR = 1.026, CI: 1.006 to 1.045, and p = 0.008). Age is the only independent predictor of poor bowel preparation amongst hospitalized patients

Développement et intégration de microcapteurs de pH et de température dans des dispositifs microfluidiques polymères

The plastics industry has been interested for some years in the possible convergence between microtechnologies and conventional polymer manufacturing (hot embossing and injection molding). In this context, this thesis aims at demonstrating the potential of a process based on microcontact printing in order to integrate metal based sensors in thermoplastic microfluidic devices shaped by hot embossing. For the mass production of thermoplastic devices, this approach appears more relevant than conventional photolithography. We chose to demonstrate this concept by investigating the integration of both a pH sensor and a temperature sensor in a thermoformed Cyclo Olefin Copolymer (COC) microfluidic system. Indeed, the measurement of these physicochemical parameters are extremely widespread in different applicative areas ranging from chemistry tobiology and medicine. For the pH sensor, we developed a pH-sensitive layer based on electrodeposited iridium oxide (IrOx) on Au. The influence of various parameters (plating solution and method , nature of the metal substrate and its method of preparation) on the pH response of these layers was studied. We were able to demonstrate that microcontact printing based on a passive approach is suitable for the preparation of pH sensors on a COC substrate with a sensitivity of -72 mV/pH and a 1 year lifetime. As regards the temperature sensor, the solution was to design a thermistor. Sensors were implemented with an approach based on active microcontact printing followed by electroless deposition of nickel (thickness varies between 0,2 and 5 μm) on polyimide. The drift of these sensors is too large for practical application. Finally, preliminary results presenting the integrating of these sensors in a fluidic microsystem are reported using an original configuration based on differential measurement of pHAfin de réaliser des dispositifs en polymère à forte valeur ajoutée, l'industrie de la plasturgie s'intéresse depuis quelques années à la convergence possible entre les microtechnologies et les méthodes industrielles de mise en oeuvre des polymères (le thermoformage et la thermo-injection). Dans ce contexte, l'objectif de cette thèse est de démontrer l'intérêt d'une approche à base de microtamponnage pour l'intégration de capteurs à base métallique dans des circuits microfluidiques en thermoplastique réalisés par thermoformage. Pour ces matériaux, cette approche apparait plus pertinente en terme de production de masse qu'une approche de photolithographie classique. Nous avons choisi de démontrer ce concept en étudiant l'intégration d'un capteur de pH et d'un capteur de température dans un système microfluidique en copolymère d'oléfine cyclique (COC) réalisé par thermoformage. En effet, la mesure de ces paramètres physico-chimiques est extrêmement répandue dans différents domaines d'application allant de la chimie à la biologie et à la médecine. Pour le capteur de pH, nous avons développé une couche sensible au pH à base d'oxyde d'iridium (IrOx) électrodéposé sur or. L'influence de différents paramètres (solution d'électrodépôt, méthode d'électrodéposition, nature du substrat métallique et son mode de préparation) sur la réponse au pH de ces couches a été étudiée. Nous avons ainsi pu démonter qu'une approche par microtamponnage passive est adaptée à la préparation de capteurs de pH sur un substrat en COC/Au ayant une sensibilité de -72 mV/pH et une durée de vie de 1 an. Pour le capteur de température, la solution retenue est basée sur le principe d'une thermorésistance. Les capteurs ont été élaborés en utilisant une approche par microtamponnage actif avec croissance d'une couche de nickel (dont l'épaisseur varie entre 0,2 et 5 μm) par métallisation autocatalytique sur polyimide. La dérive des capteurs est actuellement trop importante pour une application pratique. Finalement, des résultats préliminaires d'intégration de ces capteurs dans un microsystème fluidique thermoformé sont présentés avec notamment une configuration originale de mesure différentielle du p

Developing and integrating of pH and temperature microsensors in polymeric microfluidic devices

Afin de réaliser des dispositifs en polymère à forte valeur ajoutée, l'industrie de la plasturgie s'intéresse depuis quelques années à la convergence possible entre les microtechnologies et les méthodes industrielles de mise en oeuvre des polymères (le thermoformage et la thermo-injection). Dans ce contexte, l'objectif de cette thèse est de démontrer l'intérêt d'une approche à base de microtamponnage pour l'intégration de capteurs à base métallique dans des circuits microfluidiques en thermoplastique réalisés par thermoformage. Pour ces matériaux, cette approche apparait plus pertinente en terme de production de masse qu'une approche de photolithographie classique. Nous avons choisi de démontrer ce concept en étudiant l'intégration d'un capteur de pH et d'un capteur de température dans un système microfluidique en copolymère d'oléfine cyclique (COC) réalisé par thermoformage. En effet, la mesure de ces paramètres physico-chimiques est extrêmement répandue dans différents domaines d'application allant de la chimie à la biologie et à la médecine. Pour le capteur de pH, nous avons développé une couche sensible au pH à base d'oxyde d'iridium (IrOx) électrodéposé sur or. L'influence de différents paramètres (solution d'électrodépôt, méthode d'électrodéposition, nature du substrat métallique et son mode de préparation) sur la réponse au pH de ces couches a été étudiée. Nous avons ainsi pu démonter qu'une approche par microtamponnage passive est adaptée à la préparation de capteurs de pH sur un substrat en COC/Au ayant une sensibilité de -72 mV/pH et une durée de vie de 1 an. Pour le capteur de température, la solution retenue est basée sur le principe d'une thermorésistance. Les capteurs ont été élaborés en utilisant une approche par microtamponnage actif avec croissance d'une couche de nickel (dont l'épaisseur varie entre 0,2 et 5 μm) par métallisation autocatalytique sur polyimide. La dérive des capteurs est actuellement trop importante pour une application pratique. Finalement, des résultats préliminaires d'intégration de ces capteurs dans un microsystème fluidique thermoformé sont présentés avec notamment une configuration originale de mesure différentielle du pHThe plastics industry has been interested for some years in the possible convergence between microtechnologies and conventional polymer manufacturing (hot embossing and injection molding). In this context, this thesis aims at demonstrating the potential of a process based on microcontact printing in order to integrate metal based sensors in thermoplastic microfluidic devices shaped by hot embossing. For the mass production of thermoplastic devices, this approach appears more relevant than conventional photolithography. We chose to demonstrate this concept by investigating the integration of both a pH sensor and a temperature sensor in a thermoformed Cyclo Olefin Copolymer (COC) microfluidic system. Indeed, the measurement of these physicochemical parameters are extremely widespread in different applicative areas ranging from chemistry tobiology and medicine. For the pH sensor, we developed a pH-sensitive layer based on electrodeposited iridium oxide (IrOx) on Au. The influence of various parameters (plating solution and method , nature of the metal substrate and its method of preparation) on the pH response of these layers was studied. We were able to demonstrate that microcontact printing based on a passive approach is suitable for the preparation of pH sensors on a COC substrate with a sensitivity of -72 mV/pH and a 1 year lifetime. As regards the temperature sensor, the solution was to design a thermistor. Sensors were implemented with an approach based on active microcontact printing followed by electroless deposition of nickel (thickness varies between 0,2 and 5 μm) on polyimide. The drift of these sensors is too large for practical application. Finally, preliminary results presenting the integrating of these sensors in a fluidic microsystem are reported using an original configuration based on differential measurement of p

Crystal structure, Hirshfeld surface and reactivity of novel ligand-L-AT1 derived from dehydroacetic acid: intermolecular interactions with SARS-Cov-2/main protease

International audienceThe crystals of new ligand, namely (3E)-6-methyl-3-{1-[(pyridin-3-ylmethyl) amino] ethylene}-2H-pyran-2, 4(3H)-dione) (L-AT1), were synthesized using the evaporation solution technique. Single-crystal X-ray diffraction and physico-chemical characterization (ATR, proton and carbon-13 NMR and UV-Visible) of L-AT1 were reported. In addition, Hirshfeld surface analysis (HSA) of the solid compound, structure optimization, Mulliken and NBO charges, global indices of reactivity, local reactivity descriptors and molecular electrostatic potential (MEP) of the ligand were investigated theoretically. XRD analysis showed that L-AT1 crystallizes in the triclinic space group P-1 and the structure was stabilized through hydrogen bonds. HAS revealed that H horizontal ellipsis H (46.5%) and O horizontal ellipsis H (25.7%) contacts are in control of crystal stacking. The energy gap (4.679 eV) and reactivity descriptors indicate the stability of L-AT1. The Mulliken and NBO charges showed that the protons have a positive charge and the heteroatoms exhibit negative charges. The Fukui function and MEP study revealed that the heteroatoms are the most reactive sites for an electophilic attack on the ligand. Molecular docking simulation shows that the significant binding affinity of L-AT1 with SARS-CoV-2/Mpro is due to the formation of high number of hydrogen bonds

Dual intra- and extracellular release of monomethyl auristatin E from a neutrophil elastase-sensitive antibody-drug conjugate

International audienceAntibody-drug conjugates (ADCs) are targeted therapies, mainly used in oncology, consisting in a three-component molecular architecture combining a highly potent drug conjugated via a linker onto a monoclonal antibody (mAb), designed for the selective delivery of the drug to the tumor site. The linker is a key component, defining the ADC stability and mechanism of action, and particularly the drug release strategy. In this study, we have developed and synthesized a cleavable linker, which possesses an Asn-Pro-Val (NPV) sequence sensitive to the human neutrophil elastase (HNE), overexpressed in the tumor microenvironment. This linker permitted the site-specific conjugation of the cell-permeable drug, monomethyl auristatin E (MMAE), onto trastuzumab, using a disulfide re-bridging technology. The resulting ADC was then evaluated in vitro. This conjugate demonstrated retained antigen (Ag) binding affinity and exhibited high subnanomolar potency against Ag-positive tumor cells after internalization, suggesting an intracellular mechanism of linker cleavage. While no internalization and cytotoxic activity of this ADC was observed on Ag-negative cells in classical conditions, the supplementation of exogenous HNE permitted to restore a nanomolar activity on these cells, suggesting an extracellular mechanism of drug release in these conditions. This in vitro proof of concept tends to prove that the NPV sequence could allow a dual intra- and extracellular mechanism of drug release. This work represents a first step in the design of original ADCs with a new dual intra- and extracellular drug delivery system and opens the way to further experimentations to evaluate their full potential in vivo

GLOBAL EXISTENCE RESULTS FOR FUNCTIONAL DIFFERENTIAL INCLUSIONS WITH STATE-DEPENDENT DELAY

Our aim in this work is to study the existence of solutions of a functional differential inclusion with state-dependent delay. We use the Bohnenblust–Karlin fixed point theorem for the existence of solutions

Pancreatic surgery outcomes: multicentre prospective snapshot study in 67 countries

Background: Pancreatic surgery remains associated with high morbidity rates. Although postoperative mortality appears to have improved with specialization, the outcomes reported in the literature reflect the activity of highly specialized centres. The aim of this study was to evaluate the outcomes following pancreatic surgery worldwide.Methods: This was an international, prospective, multicentre, cross-sectional snapshot study of consecutive patients undergoing pancreatic operations worldwide in a 3-month interval in 2021. The primary outcome was postoperative mortality within 90 days of surgery. Multivariable logistic regression was used to explore relationships with Human Development Index (HDI) and other parameters.Results: A total of 4223 patients from 67 countries were analysed. A complication of any severity was detected in 68.7 percent of patients (2901 of 4223). Major complication rates (Clavien-Dindo grade at least IIIa) were 24, 18, and 27 percent, and mortality rates were 10, 5, and 5 per cent in low-to-middle-, high-, and very high-HDI countries respectively. The 90-day postoperative mortality rate was 5.4 per cent (229 of 4223) overall, but was significantly higher in the low-to-middle-HDI group (adjusted OR 2.88, 95 per cent c.i. 1.80 to 4.48). The overall failure-to-rescue rate was 21 percent; however, it was 41 per cent in low-to-middle-compared with 19 per cent in very high-HDI countries.Conclusion: Excess mortality in low-to-middle-HDI countries could be attributable to failure to rescue of patients from severe complications. The authors call for a collaborative response from international and regional associations of pancreatic surgeons to address management related to death from postoperative complications to tackle the global disparities in the outcomes of pancreatic surgery (NCT04652271; ISRCTN95140761)