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Background: Precautionary Allergen (“may contain”) Labelling (PAL) is used by industry to communicate potential risk to food-allergic individuals posed by unintended allergen presence (UAP). In 2014, the World Allergy Organization (WAO) highlighted that PAL use was increasing, but often applied inconsistently and without regulation — which reduces its usefulness to consumers with food allergy and those purchasing food for them. WAO proposed the need for a regulated, international framework to underpin application of PAL. In 2019, the World Health Organization (WHO) and the Food and Agriculture Organization (FAO) of the United Nations convened an expert consultation to address the issue of PAL, the outputs of which are now being considered by the Codex Committee on Food Labelling (CCFL). Objectives: To summarise the latest data to inform the application of PAL in a more systematic way, for implementation into global food standards. Methods: A non-systematic review of issues surrounding precautionary labelling and food allergens in pre-packaged products. Results: Approximately, 100 countries around the world have legislation on the declaration of allergenic ingredients. Just a few have legislation on UAP. Given the risks that UAP entails, non-regulated PAL creates inconvenience in real life due to its unequal, difficult interpretation by patients. The attempts made so far to rationalize PAL present lights and shadows. Conclusions: At a time when CCFL is considering the results of the FAO/WHO Expert Consultation 2020–2023, we summarise the prospects to develop an effective and homogeneous legislation at a global level, and the areas of uncertainty that might hinder international agreement on a regulated framework for PAL of food allergens.

BACKGROUND: Several studies on garlic have shown that due to its bioactive components it exhibits antimicrobial properties. The most prevalent dermatomycoses are those caused by dermatophytes and yeasts of the genus Candida. In recent years, an increase in recurrent and recalcitrant cases has been reported due to strains of dermatophytes resistant to terbinafine, a considered first-line antifungal. OBJECTIVE: The objective of this work was to determine the in-vitro antifungal effect of extracts from Chinese garlic (fresh variety) and Chilote garlic (fresh and black varieties), against the two main fungi that cause superficial mycoses: Trichophyton rubrum and Candida albicans. METHODS: Fresh garlic extracts were prepared with a hydroalcoholic method with subsequent freeze-drying. Decreasing concentrations of each extract were tested. RESULTS: Both fresh Chilote garlic and its black variety showed an antifungal effectiveness at different concentrations on both analyzed fungal agents, while white garlic of Chinese origin did not show effectiveness against C. albicans at any concentration tested. CONCLUSIONS: Black garlic, compared to fresh garlic, does not release a strong characteristic odor or flavor, which would open a point of interest as a natural alternative to the antifungals currently used. RESUMEN INTRODUCCIÓN: Numerosos estudios sobre el ajo han demostrado que, debido a sus componentes bioactivos exhibe propiedades antimicrobianas. Las dermatomicosis de mayor prevalencia son las producidas por dermatofitos y por levaduras del género Candida. En los últimos años, se ha reportado un aumento en casos recurrentes y recalcitrantes dado por cepas de dermatofitos resistentes a terbinafina, antifúngico considerado de primera línea. OBJETIVO: El objetivo del presente trabajo fue determinar el efecto antifúngico in-vitro de extractos provenientes de ajo chino (variedad fresca) y ajo chilote (variedades fresca y negra), frente a los dos principales hongos causantes de micosis superficiales: Trichophyton rubrum y Candida albicans. MÉTODOS: Los extractos de ajo fresco se realizaron con un método hidroalcohólico con posterior liofilización. Se testearon concentraciones decrecientes de cada extracto. RESULTADOS: Se observó que tanto el ajo chilote fresco como su variedad negra, poseen efectividad antifúngica para ambos agentes analizados, pero en diferentes concentraciones, mientras que el ajo blanco de origen chino no mostró efectividad frente a C. albicans en ninguna concentración testeada. CONCLUSIÓN: El ajo negro en comparación al ajo fresco, no libera un fuerte olor ni sabor característicos, lo que abriría un punto de interés como alternativa natural a los antifúngicos actualmente empleados.

Abstract Backgound Hyperoxemia is common and associated with poor outcome during veno-arterial extracorporeal membrane oxygenation (VA ECMO) support for cardiogenic shock. However, little is known about practical daily management of oxygenation. Then, we aim to describe sweep gas oxygen fraction (FSO2), postoxygenator oxygen partial pressure (PPOSTO2), inspired oxygen fraction (FIO2), and right radial arterial oxygen partial pressure (PaO2) between day 1 and day 7 of peripheral VA ECMO support. We also aim to evaluate the association between oxygenation parameters and outcome. In this retrospective multicentric study, each participating center had to report data on the last 10 eligible patients for whom the ICU stay was terminated. Patients with extracorporeal cardiopulmonary resuscitation were excluded. Primary endpoint was individual mean FSO2 during the seven first days of ECMO support (FSO2 mean (day 1−7) ). Results Between August 2019 and March 2022, 139 patients were enrolled in 14 ECMO centers in France, and one in Switzerland. Among them, the median value for FSO2 mean (day 1−7) was 70 [57; 79] % but varied according to center case volume. Compared to high volume centers, centers with less than 30 VA-ECMO runs per year were more likely to maintain FSO2 ≥ 70% (OR 5.04, CI 95% [1.39; 20.4], p = 0.017). Median value for right radial PaO2 mean (day 1−7) was 114 [92; 145] mmHg, and decreased from 125 [86; 207] mmHg at day 1, to 97 [81; 133] mmHg at day 3 (p

Magnetic polymer composites are very versatile candidates to fabricate soft robots and actuators thanks to their unique properties such as flexibility and shape memory effect. Thus, the possibility to reproduce natural shapes provides new tools for bioengineering applications. The wide panel of deformations of magnetic polymer composites can be implemented to mimic the movements and curvatures of living tissue. Herein, magnetic polymer membranes are developed to explore cell growth under curved, reversible, and controlled deformations. NdFeB/polydimethylsiloxane composite membranes (86 μm and 46 μm thick) are obtained by soft lithography and magnetized in rolled position under 3 T. Once actuated by a low magnetic field (5–86 mT), the membranes are deformed in wavy shapes with a deformation height of maximum 1.4 and 1.7 mm and a curvature radius of minimum 1.8 and 0.6 mm (86 μm and 46 μm thick membranes, respectively), for a maximum magnetic field of 86 mT. Then, Caco‐2 cell viability is studied on deformed substrates under a static (106 mT) and varying (8–78 mT) magnetic field. No increase in cell death is observed, validating a well‐characterized and promising approach for a new generation of dynamic and curved substrates for cell culture.

Heterogeneity and overuse of precautionary allergen labelling (PAL) in prepackaged foods have eroded its risk communication efficacy. Experts recommend applying PAL based on allergen concentration thresholds, but adoption remains limited. The aim of this study was to quantitatively assess the potential impact of this approach using Monte Carlo risk simulations. Four allergens and 9 food categories were considered in 2 scenarios: (1) consumption of products currently carrying PAL in Canada where individuals with food allergy (FA) are assumed to consume them, and (2) consumption of products without PAL, in a hypothetical context where PAL is applied based on thresholds that would protect 99 % (ED01) and 95 % (ED05) of individuals with FA, and individuals with FA systematically avoid products with PAL. In scenario (1), although several cases studied would cause 20 reactions/10 000 e.o. Cross-contact milk posed the highest risk (max. 1120 reactions/10 000 e.o.), and peanut, the least (max. 10 reactions/10 000 e.o.). In scenario (2), consumption of products without PAL, when using thresholds for PAL based on ED01, could lead to a maximum of 15 reactions/10 000 e. o. for all studied cases, and based on ED05, to 57 (if excluding dark chocolate with milk PAL). In most cases, the estimated number of reactions per 10 000 e.o. attributed to products with PAL currently on the market would be higher (p

Additive manufacturing is proposed as a novel tool to produce complex scaffold constructs for use in cell cultured meat. The presence of scaffolds in the final cell cultured products raises the need to understand the thermal behavior of biopolymers through culturing and cooking as it relates to the final organoleptic properties. Therefore, the objective of this study was to understand how aqueous and high temperature environments influence plasticization and contraction of biopolymer scaffolds through the physio–chemical mechanisms of hydrolysis and negative thermal expansion. To achieve this objective, scaffolds were printed using a negative thermal expansion stretch–dominated design in both PLA and PLA-TPU material configurations. The samples were evaluated after a simulated cooking experiment (90 °C for 10 mins). The formation of crystals in the single material PLA during cooking led to bend–dominated contraction while the dual-material PLA-TPU experienced stretch–dominated contraction. Furthermore, exceeding the glass transition temperature of PLA during simulated cooking in an aqueous environment caused irreversible deformation to the scaffold structure that has the potential to influence organoleptic properties.

Abstract Background Suspected upper gastrointestinal bleeding (SUGIB) is a common issue during ICU stay. In the absence of specific guidelines on the indication and timing of esophagogastroduodenoscopy (EGD), there is substantial variability in EGD indication depending on accessibility and clinical presentation. This study aimed to investigate factors associated with the need for per-EGD hemostatic therapy and to create a score predicting therapeutic benefit of emergency bedside EGD in ICU patients with SUGIB. Methods We conducted a retrospective study in our ICU to identify factors associated with the need for hemostatic procedure during EGD performed for SUGIB. From this observational cohort, we derived a score predicting the need for hemostasis during EGD, the SUGIBI score. This score was subsequently validated in a retrospective multicenter cohort. Results Two hundred fifty-five patients not primarily admitted for GI bleeding who underwent a bedside EGD for SUGIB during their ICU stay were analyzed. The preeminent EGD indication were anemia (79%), melena (19%), shock (14%), and hematemesis (13%). EGD was normal in 24.7% of cases, while primary lesions reported were ulcers (23.1%), esophagitis (18.8%), and gastritis (12.5%). Only 12.9% of patients underwent hemostatic endotherapy during EGD. A SUGIBI score

ABSTRACTSupplementation with probiotics has emerged as a promising therapeutic tool to manage metabolic diseases. We investigated the effects of a mix of Bifidobacterium animalis subsp. lactis LA804 and Lactobacillus gasseri LA806 on high-fat (HF) diet -induced metabolic disease in mice. Supplementation with the probiotic mix in HF diet-fed mice (HF-Pr2) reduced weight and fat mass gains, decreased hepatic lipid accumulation, and lowered plasma triglyceride peak during an oral lipid tolerance test. At the molecular level, the probiotic mix protected against HF-induced rise in mRNA levels of genes related to lipid uptake, metabolism, and storage in the liver and white adipose tissues, and strongly decreased mRNA levels of genes related to inflammation in the white adipose tissue and to oxidative stress in the liver. Regarding intestinal homeostasis, the probiotic mix did not prevent HF-induced gut permeability but slightly modified microbiota composition without correcting the dysbiosis induced by the HF diet. Probiotic supplementation also modified the cecal bile acid (BA) profile, leading to an increase in the Farnesoid-X-Receptor (FXR) antagonist/agonist ratio between BA species. In agreement, HF-Pr2 mice exhibited a strong inhibition of FXR signaling pathway in the ileum, which was associated with lipid metabolism protection. This is consistent with recent reports proposing that inhibition of intestinal FXR activity could be a potent mechanism to overcome metabolic disorders. Altogether, our results demonstrate that the probiotic mix evaluated, when administered preventively to HF diet-fed mice could limit obesity and associated lipid metabolism disorders, likely through the inhibition of FXR signaling in the intestinal tract.

Abstract Chronic kidney disease (CKD) is associated with osteosarcopenia, and because a physical decline in patients correlates with an increased risk of morbidity, an improvement of the musculoskeletal system is expected to improve morbi-mortality. We recently uncovered that the intestinal hormone Fibroblast Growth Factor 19 (FGF19) is able to promote skeletal muscle mass and strength in rodent models, in addition to its capacity to improve glucose homeostasis. Here, we tested the effects of a treatment with recombinant human FGF19 in a CKD mouse model, which associates sarcopenia and metabolic disorders. In 5/6 nephrectomized (5/6Nx) mice, subcutaneous FGF19 injection (0.1 mg/kg) during 18 days increased skeletal muscle fiber size independently of food intake and weight gain, associated with decreased gene expression of myostatin. Furthermore, FGF19 treatment attenuated glucose intolerance and reduced hepatic expression of gluconeogenic genes in uremic mice. Importantly, the treatment also decreased gene expression of liver inflammatory markers in CKD mice. Therefore, our results suggest that FGF19 may represent a novel interesting therapeutic strategy for a global improvement of sarcopenia and metabolic complications in CKD.

Pea is a major pulse crop in temperate regions and a model plant in genetics. Large genetic marker resources are needed to assess the genetic diversity in the species genepool and to provide selection tools for breeders. In this study, we used second-generation sequencing to perform an exome-capture protocol using a diverse pea germplasm collection, and produced a resource of over 2 million Single Nucleotide Polymorphisms. This dataset was then used to characterize the genetic diversity present in the panel and compute phylogenetic and structure analyses. The development of this resource paves the way for Genome-wide association studies and the development of powerful genotyping tools.

Abstract Biofilm (BF) growth is believed to play a major role in the development of ventilator-associated pneumonia (VAP) in the intensive care unit. Despite concerted efforts to understand the potential implication of endotracheal tube (ETT)-BF dispersal, clinically relevant data are lacking to better characterize the impact of its mesostructure and microbiological singularity on the occurrence of VAP. We conducted a multicenter, retrospective observational study during the third wave of the COVID-19 pandemic, between March and May 2021. In total, 64 ETTs collected from 61 patients were included in the present BIOPAVIR study. Confocal microscopy acquisitions revealed two main morphological aspects of ETT-deposited BF: (1) a thin, continuous ribbon-shaped aspect, less likely monobacterial and predominantly associated with Enterobacter spp., Streptococcus pneumoniae or Viridans streptococci, and (2) a thicker, discontinuous, mushroom-shaped appearance, more likely characterized by the association of bacterial and fungal species in respiratory samples. The microbiological characterization of ETT-deposited BF found higher acquired resistance in more than 80% of analyzed BF phenotypes, compared to other colonization sites from the patient’s environment. These findings reveal BF as a singular microbiological compartment, and are of added clinical value, with a view to future ETT-deposited BF-based antimicrobial stewardship in critically ill patients. Trial registration NCT04926493. Retrospectively registered 15 June 2021.

Synthetic emulsifiers promote metabolic syndrome and considerably alter gut microbiota. Data is lacking regarding natural emulsifiers like plant lecithins, a polar lipid-rich source of 18:3n-3 PUFA (ALA). For 13 weeks, male Swiss mice were fed ALA-replete semi-synthetic high-fat diet (HFD) including lecithin from rapeseed (RL) or soy, vs 2 HFD-controls devoid of lecithin (ALA-replete; low-ALA), vs Chow. Lecithins did not enhance HFD-induced adiposity nor increased inflammation, did not alter gut barrier markers and caecal bile acids, and contributed to n-3 PUFA status. Lecithins improved gut microbiota diversity. RL (10% in fat) even restored α-diversity similar to Chow, increased Lachnospiraceae NK4A136, Lactobacillus and Ruminococcaceae UCG-014 groups, and decreased Blautia genus bacteria. The abundance of most beneficial lecithin-enhanced bacteria was positively correlated to the amount of faecal polar lipid-bound ALA. These findings show that lecithins can beneficially affect the gut microbiota in association with changes in lipid residues in the distal gut.

The bacterial human pathogen Helicobacter pylori produces a type IV secretion system (cagT4SS) to inject the oncoprotein CagA into gastric cells. The cagT4SS external pilus mediates attachment of the apparatus to the target cell and the delivery of CagA. While the composition of the pilus is unclear, CagI is present at the surface of the bacterium and required for pilus formation. Here, we have investigated the properties of CagI by an integrative structural biology approach. Using Alpha Fold 2 and Small Angle X-ray scattering, it was found that CagI forms elongated dimers mediated by rod-shape N-terminal domains (CagIN) prolonged by globular C-terminal domains (CagIC). Three Designed Ankyrin Repeat Proteins (DARPins) K2, K5 and K8 selected against CagI interacted with CagIC with subnanomolar affinities. The crystal structures of the CagI:K2 and CagI:K5 complexes were solved and identified the interfaces between the molecules, thereby providing a structural explanation for the difference in affinity between the two binders. Purified CagI and CagIC were found to interact with adenocarcinoma gastric (AGS) cells, induced cell spreading and the interaction was inhibited by K2. The same DARPin inhibited CagA translocation by up to 65% in AGS cells while inhibition levels were 40% and 30% with K8 and K5, respectively. Our study suggests that CagIC plays a key role in cagT4SS-mediated CagA translocation and that DARPins targeting CagI represent potent inhibitors of the cagT4SS, a crucial risk factor for gastric cancer development.

Abstract Background Cerebral palsy (CP) associates cerebral function damages with strong locomotor defects and premature sarcopenia. We previously showed that fibroblast growth factor 19 (FGF19) exerts hypertrophic effects on skeletal muscle and improves muscle mass and strength in mouse models with muscle atrophy. Facing the lack of therapeutics to treat locomotor dysfunctions in CP, we investigated whether FGF19 treatment could have beneficial effects in an experimental rat model of CP. Methods Cerebral palsy was induced in male Wistar rat pups by perinatal anoxia immediately after birth and by sensorimotor restriction of hind paws maintained until Day 28. Daily subcutaneous injections with recombinant human FGF19 (0.1 mg/kg bw) were performed from Days 22 to 28. Locomotor activity and muscle strength were assessed before and after FGF19 treatment. At Day 29, motor coordination on rotarod and various musculoskeletal parameters (weight of tibia bone and of soleus and extensor digitorum longus (EDL) muscles; area of skeletal muscle fibres) were evaluated. In addition, expression of specific genes linked to human CP was measured in rat skeletal muscles. Results Compared to controls, CP rats had reduced locomotion activity (−37.8% of distance travelled, P

Abstract Despite decades of use of low protein diets (LPD) in the management of chronic kidney disease (CKD), their mechanisms of action are unclear. A reduced production of uremic toxins could contribute to the benefits of LPDs. Aromatic amino-acids (AA) are precursors of major uremic toxins such as p-cresyl sulfate (PCS) and indoxyl sulfate (IS). We hypothesize that a low aromatic amino acid diet (LA-AAD, namely a low intake of tyrosine, tryptophan and phenylalanine) while being normoproteic, could be as effective as a LPD, through the decreased production of uremic toxins. Kidney failure was chemically induced in mice with a diet containing 0.25% (w/w) of adenine. Mice received three different diets for six weeks: normoproteic diet (NPD: 14.7% proteins, aromatic AAs 0.019%), LPD (5% proteins, aromatic AAs 0.007%) and LA-AAD (14% proteins, aromatic AAs 0.007%). Both LPD and LA-AAD significantly reduced proteinuria, kidney fibrosis and inflammation. While LPD only slightly decreased plasma free PCS and free IS compared to NPD; free fractions of both compounds were significantly decreased by LA-AAD. These results suggest that a LA-AAD confers similar benefits of a LPD in delaying the progression of CKD through a reduction in some key uremic toxins production (such as PCS and IS), with a lower risk of malnutrition.

Abstract Introduction We conducted a nationwide Canadian telephone survey on food allergy prevalence between February 2016 and January 2017, targeting vulnerable populations (New, Indigenous, and lower-income Canadians). Objective To examine the independent effect of demographic characteristics on food allergy. Methods Canadian households with vulnerable populations were targeted using Canadian Census data and the household respondent reported whether each household member had a perceived (self-reported) or probable (self-report of a convincing history or physician diagnosis) food allergy. The association between perceived and probable food allergy and demographic characteristics was assessed through weighted multivariable random effects logistic regressions. Results Children, females, Canadian-born participants, adults with post-secondary education, and those residing in smaller households were more likely to report perceived or probable food allergy. Although immigrant parents self-reported less food allergy, Canadian-born children of Southeast/East Asian immigrant versus other immigrant or Canadian-born parents reported more food allergy. Conclusion We have demonstrated clear associations between demographic characteristics and food allergy, which may provide important clues to the environmental determinants of food allergy.

Abstract Most Canadian food allergy data has focused on Health Canada’s priority food allergens. This study describes which non-priority (emerging) food allergens were most commonly reported by Canadian parents and categorized/confirmed by allergists. A secondary aim was to describe severity of allergic reactions to emerging allergens. Parents reported allergic reactions to emerging food allergens experienced by their child (

Southeast Asia is marked by its diversity and, unfortunately, widespread ethnic conflict and political instability. This unsafe environment has led members of vulnerable ethnic groups, particularly those who reside in mountainous upland regions, to engage in refugee movements throughout the region. Yale political scientist James C. Scott discusses this particular subset of upland migrants in his book, The Art of Not Being Governed. He characterizes the interactions between the upland and lowland peoples as one where the former seeks to escape state control and official legibility from the latter. The Dara’ang are one such upland group seeking relocation. Since the 1990s, thousands of Dara’ang have fled Myanmar into Northern Thailand in a seemingly Scottsian pattern. This paper argues, however, that the Dara’ang exhibit shifting attitudes toward state control and legibility—from one of escaping the state to one of embracing the state in search of an improved quality of life. Data for this paper was collected through archival research and fieldwork in Thailand and Myanmar in 2018. Inclusive of qualitative interviews and observational data, the paper analyzes collected evidence against Scott’s theoretical framework to modify Scott’s conclusions, at least with respect to the experience of Dara’ang refugees.

Background: Palliative care teams face complex medical situations on a daily basis. These situations require joint reflection and decision making to propose appropriate patient care. Sometimes, sedation is one of the options to be considered. In addition to medical and technical criteria justifying the use of sedation, multiple psychosocial criteria impact the decision making of palliative care teams and guide, give sense to, and legitimize professional practices. Objective: The main goal of this study was to explore perceptions, experiences, and beliefs of palliative care teams about sedation practices in a legislative context (Claeys?Leonetti law, 2016; France), which authorizes continuous deep sedation (CDS) until death. Methods: This is a qualitative study using 28 semistructured interviews with physicians and nurses working in a palliative care team in France (PACA region). All verbal productions produced during interviews were fully transcribed and the contents analyzed. Findings: Content analysis revealed four themes: (1) sedation as a ?good death,? (2) emotional experiences of sedations, (3) the practice of CDS, and (4) the ambiguous relationship with the Claeys?Leonetti law. Conclusions: This qualitative study provides evidence of a form of ?naturalization? of the practice of sedation. However, the Claeys?Leonetti law exacerbates differences of opinion between palliative caregivers on sedation and questions the interest of this law for society and palliative care practices. clinicalTrials.gov identifier: NCT04016038.

Abstract Precautionary allergen labeling (PAL) is widely used by food industries. Occurrence studies revealed that few analyzed products contained the allergen(s) present in the statement, but little is known in Canada. To improve manufacturing practices and better manage allergen cross-contamination, occurrence data is needed to determine the exposure of allergic individuals eating those products. Samples were analyzed for peanuts (n = 871) and hazelnuts (n = 863) using ELISA methods. Within samples analyzed for peanuts, 72% had a PAL (n = 628), 1% had peanuts as a minor ingredient (n = 9) and 27% were claimed “peanut-free” (n = 234). Most hazelnut samples had a PAL for tree nuts/hazelnuts (94%; n = 807) with 6% claimed “nut-free” (n = 56). Peanuts and hazelnuts were found in 4% (0.6–28.1 ppm) and 9% (0.4–2167 ppm) of all samples, respectively. Chocolates were mostly impacted; they should be treated apart from other foods and used in risk assessments scenarios to improve manufacturing practices, reducing unnecessary PAL use.

Abstract Background Little is known on the outcome and risk factors for mortality of patients admitted in Intensive Care units (ICUs) for Acute cholangitis (AC). Methods Retrospective multicenter study included adults admitted in eleven intensive care units for a proven AC from 2005 to 2018. Risk factors for in-hospital mortality were identified using multivariate analysis. Results Overall, 382 patients were included, in-hospital mortality was 29%. SOFA score at admission was 8 [5–11]. Biliary obstruction was mainly related to gallstone (53%) and cancer (22%). Median total bilirubin and PCT were respectively 83 µmol/L [50–147] and 19.1 µg/L [5.3–54.8]. Sixty-three percent of patients (n = 252) had positive blood culture, mainly Gram-negative bacilli (86%) and 14% produced extended spectrum beta lactamase bacteria. At ICU admission, persisting obstruction was frequent (79%) and biliary decompression was performed using therapeutic endoscopic retrograde cholangiopancreatography (76%) and percutaneous transhepatic biliary drainage (21%). Adjusted mortality significantly decreased overtime, adjusted OR for mortality per year was 0.72 [0.54–0.96] (p = 0.02). In a multivariate analysis, factors at admission associated with in-hospital mortality were: SOFA score (OR 1.14 [95% CI 1.05–1.24] by point, p = 0.001), lactate (OR 1.21 [95% CI 1.08–1.36], by 1 mmol/L, p 48 h was associated with in-hospital mortality (adjusted OR 2.73 [95% CI 1.30–6.22], p = 0.02). Conclusions In this large retrospective multicenter study, we found that AC-associated mortality significantly decreased overtime. Severity of organ failure, cause of obstruction and local complications of AC are risk factors for mortality, as well as delayed biliary drainage > 48 h.

Abstract Background Viral infections are common complications following allogeneic hematopoietic stem cell transplantation (allo-HSCT). Allo-HSCT recipients with steroid-refractory/dependent graft-versus-host disease (GvHD) are highly immunosuppressed and are more vulnerable to infections with weakly pathogenic or commensal viruses. Here, twenty-five adult allo-HSCT recipients from 2016 to 2019 with acute or chronic steroid-refractory/dependent GvHD were enrolled in a prospective cohort at Geneva University Hospitals. We performed metagenomics next-generation sequencing (mNGS) analysis using a validated pipeline and de novo analysis on pooled routine plasma samples collected throughout the period of intensive steroid treatment or second-line GvHD therapy to identify weakly pathogenic, commensal, and unexpected viruses. Results Median duration of intensive immunosuppression was 5.1 months (IQR 5.5). GvHD-related mortality rate was 36%. mNGS analysis detected viral nucleotide sequences in 24/25 patients. Sequences of ≥ 3 distinct viruses were detected in 16/25 patients; Anelloviridae (24/25) and human pegivirus-1 (9/25) were the most prevalent. In 7 patients with fatal outcomes, viral sequences not assessed by routine investigations were identified with mNGS and confirmed by RT-PCR. These cases included Usutu virus (1), rubella virus (1 vaccine strain and 1 wild-type), novel human astrovirus (HAstV) MLB2 (1), classic HAstV (1), human polyomavirus 6 and 7 (2), cutavirus (1), and bufavirus (1). Conclusions Clinically unrecognized viral infections were identified in 28% of highly immunocompromised allo-HSCT recipients with steroid-refractory/dependent GvHD in consecutive samples. These identified viruses have all been previously described in humans, but have poorly understood clinical significance. Rubella virus identification raises the possibility of re-emergence from past infections or vaccinations, or re-infection. Video abstract

Wang et al. show how genetic sequence and base modifications can be detected simultaneously on single molecules of both DNA and RNA using magnetic tweezers. They also demonstrate an amplification-free CRISPR/Cas9-based strategy for isolating target regions from native DNA and apply this approach to the isolation of targets from E. coli and human genomic DNA.

Viral infections are the leading cause of childhood acute febrile illnesses motivating consultation in sub-Saharan Africa. The majority of causal viruses are never identified in low-resource clinical settings as such testing is either not part of routine screening or available diagnostic tools have limited ability to detect new/unexpected viral variants. An in-depth exploration of the blood virome is therefore necessary to clarify the potential viral origin of fever in children. Metagenomic next-generation sequencing is a powerful tool for such broad investigations, allowing the detection of RNA and DNA viral genomes. Here, we describe the blood virome of 816 febrile children (

The ageing of population is increasing, and a great percentage of these patients wear removable prostheses, and can suffer denture stomatitis, a condition that has been associated with candidiasis. Aims: To evaluate in vitro the effectiveness of Copper Sulfate against Candida albicans in samples of heat-polymerized acrylic resin, compared to nystatin, sodium hypochlorite and chlorhexidine. Materials and Methods: Initially, the minimum inhibitory concentration (MIC) of copper sulfate for Candida albicans was determined by microdilution. Then, 54 resin samples were divided into 6 treatment groups corresponding to Nystatin 100.000 UI, Sodium Hypochlorite 0.5%, chlorhexidine 0.12%, Copper Sulfate 4.7µg/ml, Copper Sulfate 9.4µg/ml and physiological saline solution, in which samples were submerged for 6 hours. Resin samples were then washed and cultured on solid media at 37°C for 72 hours. The number of colony-forming units was determined using a Quebec colony counter. The statistical analysis was performed using the Kruskal-Wallis test and the Mann-Whitney U test. Results: Copper sulfate at a concentration of 9.4μg/ml presented a similar effectiveness as the other control products regarding the reduction in the number of colonies of Candida albicans post-treatment. Conclusion: The effectiveness of copper sulfate against Candida albicans on acrylic resin was similar to that of nystatin, sodium hypochlorite and chlorhexidine.

Abetalipoproteinemia (FHBL-SD1) and chylomicron retention disease (FHBL-SD3) are rare recessive disorders of lipoprotein metabolism due to mutations in MTTP and SAR1B genes, respectively, which lead to defective chylomicron formation and secretion. This results in lipid and fat-soluble vitamin malabsorption, which induces severe neuro-ophthalmic complications. Currently, treatment combines a low-fat diet with high-dose vitamin A and E supplementation but still fails in normalizing serum vitamin E levels and providing complete ophthalmic protection. To explore these persistent complications, we developed two knock-out cell models of FHBL-SD1 and FHBL-SD3 using the CRISPR/Cas9 technique in Caco-2/TC7 cells. DNA sequencing, RNA quantification and Western blotting confirmed the introduction of mutations with protein knock-out in four clones associated with i) impaired lipid droplet formation and ii) defective triglyceride (−57.0 ± 2.6% to −83.9 ± 1.6%) and cholesterol (−35.3 ± 4.4% to −60.6 ± 3.5%) secretion. A significant decrease in α-tocopherol secretion was also observed in these clones (−41.5 ± 3.7% to −97.2 ± 2.8%), even with the pharmaceutical forms of vitamin E: tocopherol-acetate and tocofersolan (α-tocopheryl polyethylene glycol succinate 1000). MTTP silencing led to a more severe phenotype than SAR1B silencing, which is consistent with clinical observations. Our cellular models thus provide an efficient tool to experiment with therapeutic strategies and will allow progress in understanding the mechanisms involved in lipid metabolism.

A Correction to this paper has been published: https://doi.org/10.1038/s42003-021-01894-9

ABSTRACTFever is the leading cause of paediatric outpatient consultations in Sub-Saharan Africa. Although most are suspected to be of viral origin, a putative causative pathogen is not identified in over a quarter of these febrile episodes. Using a de novo assembly sequencing approach, we report the detection (15.4%) of dicistroviruses (DicV) RNA in sera collected from 692 febrile Tanzanian children. In contrast, DicV RNA was only detected in 1/77 (1.3%) plasma samples from febrile Tanzanian adults, suggesting that children could represent the primary susceptible population. Estimated viral load by specific quantitative real-time RT–PCR assay ranged from < 1.32E3 to 1.44E7 viral RNA copies/mL serum. Three DicV full-length genomes were obtained, and a phylogenetic analyse on the capsid region showed the presence of two clusters representing tentative novel genus. Although DicV-positive cases were detected throughout the year, a significantly higher positivity rate was observed during the rainy season.This study reveals that novel DicV RNA is frequently detected in the blood of Tanzanian children, paving the way for further investigations to determine if DicV possibly represent a new agent in humans.

Renal ischemia-reperfusion (IR) injury can lead to acute kidney injury, increasing the risk of developing chronic kidney disease. We hypothesized that mild therapeutic hypothermia (mTH), 34 °C, applied during ischemia could protect the function and structure of kidneys against IR injuries in mice. In vivo bilateral renal IR led to an increase in plasma urea and acute tubular necrosis at 24 h prevented by mTH. One month after unilateral IR, kidney atrophy and fibrosis were reduced by mTH. Evaluation of mitochondrial function showed that mTH protected against IR-mediated mitochondrial dysfunction at 24 h, by preserving CRC and OX-PHOS. mTH completely abrogated the IR increase of plasmatic IL-6 and IL-10 at 24 h. Acute tissue inflammation was decreased by mTH (IL-6 and IL1-β) in as little as 2 h. Concomitantly, mTH increased TNF-α expression at 24 h. One month after IR, mTH increased TNF-α mRNA expression, and it decreased TGF-β mRNA expression. We showed that mTH alleviates renal dysfunction and damage through a preservation of mitochondrial function and a modulated systemic and local inflammatory response at the acute phase (2–24 h). The protective effect of mTH is maintained in the long term (1 month), as it diminished renal atrophy and fibrosis, and mitigated chronic renal inflammation.