Unusual cause of mechanical ileus: abdominal cocoon syndrome

A 38-year-old black male patient was admitted with diarrhea and nausea over two days and aggravating pain in the meso- and epigastium that resolved after urination. He had no surgical history and only an episode of pulmonary tuberculosis five years earlier, for which he was properly treated. Physical examination revealed a tender and distended abdomen with clangorous sounds. His temperature was 36.1°C. Routine laboratory blood analyses were normal. An abdominal ultrasound revealed diffuse distention of the small intestine. A computed tomography (CT) scan showed a conglomerate of dilated small bowel loops in the meso- and hypogastrium, suggestive for a supravesical mechanical small bowel obstruction. Peritoneal thickening was seen in the right epigastrium (Figure A, white arrow). An explorative laparoscopy revealed a whitish, thickened membrane encapsulating the small bowels as a ‘cocoon’ (Figure B). Extensive adhesiolysis released an intestinal kinking in the lower abdomen, just above the bladder. No resection was needed. Histopathology of the membrane showed fibrocollagenous tissue with mixed inflammatory infiltrate

The Effect of a Multifaceted Intervention Including Classroom Education and Bariatric Weight Suit Use on Medical Students' Attitudes toward Patients with Obesity

INTRODUCTION Weight bias refers to negative attitudes toward individuals because of their weight. Evidence-based strategies to successfully reduce weight bias in medical students are lacking. The purpose of this study was to investigate the impact of a multifaceted intervention on medical students' attitudes toward patients with obesity. METHODS Third and fourth year medical students (n = 79), who enrolled in an 8-week graduate course focusing on the various epidemiologic, physiological, and clinical aspects of obesity, including a gamification task with bariatric weight suits (BWSs), were asked to complete the Nutrition, Exercise and Weight Management (NEW) Attitudes Scale questionnaire pre- and post-course. The inclusion period was between September 2018 and June 2021 and covered 4 consecutive groups of students. RESULTS The overall NEW Attitudes Scale scores did not change significantly pre- versus post-intervention (pre-course: 19.59, post-course: 24.21, p value = 0.24). However, the subgroup of 4th year medical students showed a significant improvement in their attitudes (pre-course: 16.4, post-course: 26.16, p value = 0.02). The Thurstone rating of 9 out of 31 individual survey items changed significantly from pre- to post-course with a moderate strength (Cramer's V >0.2), including 5 items showing weight bias reduction. The disagreement with the statement "overweight/obese individuals lack willpower" increased from 37 to 68%. CONCLUSION These findings suggest that in medical students with a low level of weight bias at baseline, a semester course on obesity combined with BWS use affects only a limited number of items of the NEW Attitudes Scale questionnaire. The sensitization of medical students to weight stigma has the potential to improve quality of healthcare for patients with obesity

Case Report:Bosentan and Sildenafil Exposure in Human Milk - A Contribution From the ConcePTION Project

Introduction: Quantitative information on disposition of maternal medicines in human milk remains a major knowledge gap. This case report presents the clinical and pharmacokinetic data of a single mother-infant pair exposed to bosentan and sildenafil for the treatment of pulmonary arterial hypertension (PAH) during lactation. Case presentation: A 43-year old mother was treated with sildenafil (20 mg, 3x/day) and bosentan (125 mg, 2x/day) for PAH. Her 21-months old infant received breastfeeding in combination with adequate complementary foods. Milk samples were collected over 24 h, at day 637 and 651 after delivery. The observed average steady-state concentrations of sildenafil (2.84 μg/L) and bosentan (49.0 μg/L) in human milk were low. The Daily Infant Dosage ingested by the nursing infant through human milk was 0.02 μg/kg/day for sildenafil and 0.29 μg/kg/day for bosentan at day 637, and 0.03 μg/kg/day and 0.60 μg/kg/day at day 651. The Relative Infant Dose calculated for an exclusively breastfed infant with an estimated milk intake of 150 ml/kg/day, was 0.06% for sildenafil and 0.24% for bosentan. General health outcome of the infant, reported by the mother, was uneventful until the sampling days. Conclusion: Low medicine concentrations were found in human milk expressed 21 months after delivery after maternal intake of 20 mg sildenafil three times daily and 125 mg bosentan twice daily. General health of the nursing infant until sampling was reported as optimal by the mother

Development of a pig mammary epithelial cell culture model as a non‐clinical tool for studying epithelial barrier— a contribution from the imi‐conception project

The ConcePTION project aims at generating further knowledge about the risks related to the use of medication during breastfeeding, as this information is lacking for most commonly used drugs. Taking into consideration multiple aspects, the pig model has been considered by the consortium as the most appropriate choice. The present research was planned to develop an efficient method for the isolation and culture of porcine Mammary Epithelial Cells (pMECs) to study the mammary epithelial barrier in vitro. Mammary gland tissues were collected at a local slaughterhouse, dissociated and the selected cellular population was cultured, expanded and characterized by morphology, cell cycle analysis and immunophenotyping. Their ability to create a barrier was tested by TEER measurement and sodium fluorescein transport activity. Expression of 84 genes related to drug transporters was evaluated by a PCR array. Our results show that primary cells express epithelial cell markers: CKs, CK18, E‐Cad and tight junctions molecules ZO‐1 and OCL. All the three pMEC cellular lines were able to create a tight barrier, although with different strengths and kinetics, and express the main ABC and SLC drug transporters. In conclusion, in the present paper we have reported an efficient method to obtain primary pMEC lines to study epithelial barrier function in the pig model

A comprehensive review on non-clinical methods to study transfer of medication into breast milk – A contribution from the ConcePTION project

open17siBreastfeeding plays a major role in the health and wellbeing of mother and infant. However, information on the safety of maternal medication during breastfeeding is lacking for most medications. This leads to discontinuation of either breastfeeding or maternal therapy, although many medications are likely to be safe. Since human lactation studies are costly and challenging, validated non-clinical methods would offer an attractive alternative. This review gives an extensive overview of the non-clinical methods (in vitro, in vivo and in silico) to study the transfer of maternal medication into the human breast milk, and subsequent neonatal systemic exposure. Several in vitro models are available, but model characterization, including quantitative medication transport data across the in vitro blood-milk barrier, remains rather limited. Furthermore, animal in vivo models have been used successfully in the past. However, these models don't always mimic human physiology due to species-specific differences. Several efforts have been made to predict medication transfer into the milk based on physicochemical characteristics. However, the role of transporter proteins and several physiological factors (e.g., variable milk lipid content) are not accounted for by these methods. Physiologically-based pharmacokinetic (PBPK) modelling offers a mechanism-oriented strategy with bio-relevance. Recently, lactation PBPK models have been reported for some medications, showing at least the feasibility and value of PBPK modelling to predict transfer of medication into the human milk. However, reliable data as input for PBPK models is often missing. The iterative development of in vitro, animal in vivo and PBPK modelling methods seems to be a promising approach. Human in vitro models will deliver essential data on the transepithelial transport of medication, whereas the combination of animal in vitro and in vivo methods will deliver information to establish accurate in vitro/in vivo extrapolation (IVIVE) algorithms and mechanistic insights. Such a non-clinical platform will be developed and thoroughly evaluated by the Innovative Medicines Initiative ConcePTION.openNauwelaerts N.; Deferm N.; Smits A.; Bernardini C.; Lammens B.; Gandia P.; Panchaud A.; Nordeng H.; Bacci M.L.; Forni M.; Ventrella D.; Van Calsteren K.; DeLise A.; Huys I.; Bouisset-Leonard M.; Allegaert K.; Annaert P.Nauwelaerts N.; Deferm N.; Smits A.; Bernardini C.; Lammens B.; Gandia P.; Panchaud A.; Nordeng H.; Bacci M.L.; Forni M.; Ventrella D.; Van Calsteren K.; DeLise A.; Huys I.; Bouisset-Leonard M.; Allegaert K.; Annaert P

3D printing is a transformative technology in congenital heart disease

Survival in congenital heart disease has steadily improved since 1938, when Dr. Robert Gross successfully ligated for the first time a patent ductus arteriosus in a 7-year-old child. To continue the gains made over the past 80 years, transformative changes with broad impact are needed in management of congenital heart disease. Three-dimensional printing is an emerging technology that is fundamentally affecting patient care, research, trainee education, and interactions among medical teams, patients, and caregivers. This paper first reviews key clinical cases where the technology has affected patient care. It then discusses 3-dimensional printing in trainee education. Thereafter, the role of this technology in communication with multidisciplinary teams, patients, and caregivers is described. Finally, the paper reviews translational technologies on the horizon that promise to take this nascent field even further

A comprehensive review on non-clinical methods to study transfer of medication into breast milk – A contribution from the ConcePTION project

Breastfeeding plays a major role in the health and wellbeing of mother and infant. However, information on the safety of maternal medication during breastfeeding is lacking for most medications. This leads to discontinuation of either breastfeeding or maternal therapy, although many medications are likely to be safe. Since human lactation studies are costly and challenging, validated non-clinical methods would offer an attractive alternative. This review gives an extensive overview of the non-clinical methods (in vitro, in vivo and in silico) to study the transfer of maternal medication into the human breast milk, and subsequent neonatal systemic exposure. Several in vitro models are available, but model characterization, including quantitative medication transport data across the in vitro blood-milk barrier, remains rather limited. Furthermore, animal in vivo models have been used successfully in the past. However, these models don't always mimic human physiology due to species-specific differences. Several efforts have been made to predict medication transfer into the milk based on physicochemical characteristics. However, the role of transporter proteins and several physiological factors (e.g., variable milk lipid content) are not accounted for by these methods. Physiologically-based pharmacokinetic (PBPK) modelling offers a mechanism-oriented strategy with bio-relevance. Recently, lactation PBPK models have been reported for some medications, showing at least the feasibility and value of PBP

Development of a hydrometallurgical route for the production of high-purity indium

Indium is essential for many electronic applications, e.g. photovoltaics and laptops. Due to the increasing demand for indium in high-tech applications and China’s dominance in the indium production, this metal is labelled as a critical raw material by the European Commission. To keep pace with the increasing demand, efficient industrial processes for the recovery of indium from ore-processing by-products and end-of-life consumer goods must be developed. The Umicore Precious Metals Refining business unit at Hoboken (Belgium) produced 4N5 indium metal. This recycling process was quite energy- and time-consuming, had a low efficiency and yielded indium metal with fluctuating purity levels. Therefore, the production process is stopped halfway between the raw materials and pure indium metal, manufacturing an intermediate crude indium(III) hydroxide (In(OH)3, containing 80–90% indium). Given Umicore’s drive towards sustainable development, the aim of this PhD thesis is to design an alternative sustainable indium refinery process for the production of high-purity indium (5N) starting from crude In(OH)3. This will be done by developing several new hydrometallurgical unit processes and combining them into a new process flowsheet. With the aim of developing a sustainable refining process, ionic liquids are taken into account. This PhD thesis shows how ionic liquids can be used as green alternative solvents to replace the conventional aqueous or organic solvents in the leaching, solvent extraction and electrowinning stages. In a first approach, the extraction of indium from chloride media by the commercially available ionic liquids Cyphos IL 101 and Aliquat 336 is presented. High percentages extraction, high loadings and fast kinetics make these solvent extraction systems very suitable for extraction of indium. Indium was recovered as In(OH)3 by precipitation stripping with NaOH, regenerating the ionic liquid at the same time. Moreover, the extraction process was selective for In(III), over many other metal ions (As(III), Mn(II), Ni(II), Cu(II)) that are commonly found as impurities in process solutions of indium refineries. Cd(II), Fe(III), Pb(II), Sn(IV) and Zn(II) were co-extracted to the ionic liquid phase. Speciation of indium complexes in the aqueous and ionic liquid phase can provide more insight in the extraction mechanism and allows proper tuning of conditions and selection of extractants. In an aqueous HCl solution (0–12 M), indium(III) exists as mixed octahedral complexes, [In(H2O)6–nCln]3–n (0 ≤ n ≤ 6), while in the ionic liquid phase indium(III) is present as the tetrahedral [InCl4]– unaffected by the HCl concentration in the aqueous phase. An extraction mechanism was proposed based on the speciation studies in which indium(III) can be extracted as a neutral complex, In(H2O)3Cl3. In a second approach, a combined leaching/extraction system was proposed for the selective recovery of indium from crude In(OH)3 based on the thermomorphic and acidic properties of the ionic liquid [Hbet][Tf2N]. Efficient indium leaching was obtained by a 1:1 wt/wt [Hbet][Tf2N]–H2O mixture. The formation of a biphasic system induced metal separation where In(III) is extracted to the ionic liquid phase, whereas Al(III), Ca(II), Cd(II), Ni(II) and Zn(II) remain in the aqueous phase. Fe(III), As(V) and Pb(II) are co-extracted to the ionic liquid phase. Iron remained in the aqueous phase by addition of ascorbic acid to the aqueous phase, thereby reducing Fe(III) to Fe(II). A HCl solution was used to strip indium(III) to the aqueous phase, regenerating at the same time the ionic liquid. By combining a prehydrolysis and hydrolysis step on the aqueous phase obtained after stripping, the purity of the crude In(OH)3 was improved. In a final approach, Cyphos IL 101 was used as an electrolyte for the recovery of indium by electrodeposition at elevated temperatures. Indium is electrochemically reduced from In(III) to In(I) and subsequently from In(I) to In(0). Droplet-like deposits were observed between 100 and 180 °C, but their origin is not clear yet: melting-point depression of very small primary indium particles in combination with undercooling or dewetting. Also, droplet-on-droplet deposition took place indicating that there is a surface indium oxide layer present preventing the droplets to coalesce. Moreover, the electrowinning process was selective for In(III) over Zn(II). High-temperature electrowinning requires thermally stable electrolytes. The thermal stability of Cyphos IL 101 was investigated, both by dynamic and static TGA. Dynamic TGA overestimated the real thermal stability, while addition of metal chlorides to the ionic liquid increased the thermal stability. It was shown that Cyphos IL 101 had a long-term thermal stability at 180 °C in an inert atmosphere.ACKNOWLEDGEMENT ABSTRACT SAMENVATTING ABBREVIATIONS AND SYMBOLS TABLE OF CONTENT THESIS OUTLINE CHAPTER 1: INTRODUCTION 1.1 Indium 1.2 Hydrometallurgy as a tool for metal recovery 1.2.1 Leaching 1.2.2 Precipitation and cementation 1.2.3 Solvent extraction 1.2.4 Electrochemistry 1.3 Ionic liquids in hydrometallurgy 1.3.1 Processing of minerals and metal oxides 1.3.2 Separation of metals using solvent extraction 1.3.3 Electrodeposition of metals in ionic liquids 1.4 Indium recovery 1.4.1 Indium recovery from primary and secondary sources 1.4.2 Ionic liquid technology for indium recovery 1.4.3 Indium recovery at Umicore 1.5 References CHAPTER 2: OBJECTIVES CHAPTER 3: PURIFICATION OF INDIUM BY SOLVENT EXTRACTION WITH UNDILUTED IONIC LIQUIDS 3.1 Introduction 3.2 Experimental 3.2.1 Chemicals 3.2.2 Instrumentation and analysis methods 3.2.3 Extraction experiments 3.2.4 Mono-element system 3.2.5 Multi-element system 3.3 Results and discussion 3.3.1 Mono-element system 3.3.2 Multi-element system 3.4 Conclusions 3.5 References 3.6 Supplementary information CHAPTER 4: SPECIATION OF INDIUM(III) CHLORO COMPLEXES IN THE SOLVENT EXTRACTION PROCESS FROM CHLORIDE AQUEOUS SOLUTIONS TO IONIC LIQUIDS 4.1 Introduction 4.2 Experimental 4.2.1 Chemicals 4.2.2 Instrumentation and analysis methods 4.2.3 Solvent extraction 4.2.4 Distribution ratio 4.3 Results and discussion 4.3.1 Indium(III) speciation in the aqueous phase 4.3.2 Solvent extraction of indium(III) 4.3.3 Indium(III) speciation in the ionic liquid phase 4.3.4 Solvent extraction mechanism 4.4 Conclusions 4.5 References 4.6 Supplementary information CHAPTER 5: PURIFICATION OF CRUDE IN(OH)3 USING THE FUNCTIONALIZED IONIC LIQUID BETAINIUM BIS(TRIFLUOROMETHYLSULFONYL)IMIDE 5.1 Introduction 5.2 Experimental 5.2.1 Chemicals 5.2.2 Instrumentation and analysis methods 5.2.3 Synthesis of [Hbet][Tf2N] 5.2.4 Leaching 5.2.5 Quantitative 1H NMR 5.2.6 Scrubbing 5.2.7 Stripping 5.3 Results and discussion 5.3.1 Leaching of crude In(OH)3 in [Hbet][Tf2N] 5.3.2 Thermomorphic leaching/extraction in a [Hbet][Tf2N]–H2O system 5.3.3 Metal scrubbing/stripping and recovery of ionic liquid 5.4 Conclusions 5.5 References 5.6 Supplementary information CHAPTER 6: THERMAL STABILITY OF TRIHEXYL(TETRADECYL)PHOSPHONIUM CHLORIDE 6.1 Introduction 6.2 Experimental 6.2.1 Chemicals 6.2.2 Instrumentation and analysis methods 6.2.3 Cyphos IL 101 Purification 6.3 Results and discussion 6.3.1 Short-term stability 6.3.2 Long-term stability 6.3.3 Decomposition products 6.4 Conclusions 6.5 References 6.6 Supplementary information CHAPTER 7: ELECTRODEPOSITION OF INDIUM FROM THE IONIC LIQUID TRIHEXYL(TETRADECYL)PHOSPHONIUM CHLORIDE 7.1 Introduction 7.2 Experimental 7.2.1 Chemicals 7.2.2 Instrumentation and analysis methods 7.2.3 Cyphos IL 101 Purification 7.3 Results and discussion 7.3.1 Electrochemical study in commercial Cyphos IL 101 7.3.2 Electrochemical stability of purified Cyphos IL 101 7.3.3 Electrochemical study of indium on Mo and Pt in purified Cyphos IL 101 7.3.4 Electrochemical study of zinc and iron on Mo in purified Cyphos IL 101 7.3.5 Diffusion coefficient of indium in purified Cyphos IL 101 7.4 Conclusions 7.5 References 7.6 Supplementary information CHAPTER 8: FLOWSHEET DESIGN 8.1 Introduction 8.2 Experimental 8.2.1 Chemicals 8.2.2 Instrumentation and analysis methods 8.2.3 Leaching 8.2.4 Solvent extraction 8.3 Results and discussion 8.3.1 Leaching 8.3.2 Solvent extraction 8.3.3 Electrowinning 8.3.4 Flowsheet design 8.4 Conclusions 8.5 References CHAPTER 9: CONCLUSIONS AND OUTLOOK HEALTH, SAFETY & ENVIRONMENT LIST OF PUBLICATIONS LIST OF CONFERENCESnrpages: 284status: publishe