Effects of saffron extract supplementation on mood, well-being, and response to a psychosocial stressor in healthy adults: A randomized, double-blind, parallel group, clinical trial

Anxiety, stress, and low mood are closely related and may contribute to depressive symptoms. Among non-pharmacological solutions to improve subclinical mood symptoms and resilience to stress, natural products such as saffron—identified as promising following preliminary beneficial effects in major depressive disorder—represent a relevant strategy. This study aimed to assess the efficacy of 8 weeks' supplementation with 30 mg standardized saffron extract on emotional well-being in healthy adults with subclinical feelings of low mood and anxiety and/or stress and evaluate the acute effect of saffron in response to a lab-based psychosocial stressor. The study adopted a double-blind, randomized, parallel groups design in which 56 healthy male and female individuals (18–54 years) received either a saffron extract or a placebo for 8 weeks. Chronic effects of saffron on subjective anxiety, stress, and depressive feelings were assessed using a questionnaire battery [including Profile of Mood State-2, (POMS)] and acute effects in response to a lab-based psychosocial stressor were measured through psychological and physiological parameters. Urinary crocetin levels were quantified. Participants who received the saffron extract reported reduced depression scores and improved social relationships at the end of the study. Urinary crocetin levels increased significantly with saffron supplementation and were correlated with change in depression scores. The typical stress-induced decrease in heart rate variability (HRV) during exposure to the stressor was attenuated following acute saffron intake. Saffron extract appears to improve subclinical depressive symptoms in healthy individuals and may contribute to increased resilience against the development of stress-related psychiatric disorders. Clinical trials number: NCT03639831

The tree that hides the forest: identification of common predisposing loci in several hematopoietic cancers and several dog breeds

Histiocytic sarcoma (HS) is a rare but aggressive cancer in humans and dogs. The spontaneous canine model, with the clinical, epidemiological and histological similarities with human HS and specific breed predispositions, is a unique model/opportunity to unravel the genetic bases of this cancer. In this study, we aimed to identify germline risk factors associated with the development of HS in canine predisposed breeds. We used a methodology that combined several genome-wide association studies in a multi-breed and multi-cancer approach, as well as targeted next generation sequencing, and imputation combining several breeds (Bernese mountain dog, Rottweiler, flat coated retriever and golden retriever) and three haematopoietic cancers (HS, lymphoma and mast cell tumor). Results showed that we not only refined the previously identified HS risk CDKN2A locus but we identified new loci on canine chromosomes 2, 5, 12, 14, 20, 26 and X. Capture and targeted sequencing of specific loci pointed towards the existence of regulatory variants in non coding regions and/or methylation mechanisms linked to risk haplotypes, leading to strong cancer predispositions in specific dog breeds. Our results showed that these canine cancer predisposing loci appear to be due to the additive effect of several risk haplotype involved also in other haematopoietic cancers such lymphoma or mast cell tumor, illustrating the pleiotropic nature of these canine cancer loci as observed in human oncology, thus reinforcing the interest of predisposed dog breeds to study cancer initiation and progression

Latissimus Dorsi Flap Invasion by Ductal Breast Carcinoma after Lipofilling

Summary: Autologous fat grafting is commonly performed in reconstructive breast surgery but also increasingly in breast augmentation surgery. On the international level, we are witnessing an important increased confidence for this procedure. Nevertheless, it continues to raise questions on the risks of cancer. A 66-year-old patient benefited from a lipofilling to improve a latissimus dorsi flap breast reconstruction, 7 years after initial cancer management. Two years later, constant pain in the flap leads to reoperation. The flap showed a major retraction with histologically massive infiltration of the muscle by an undifferentiated carcinoma of breast origin. The tumor cells were displayed directly in contact with lipofilling inside the muscle. Without establishing any causal link between these 2 events, this case raises the question once more of the risks of breast cancer and encourages us to continue being careful

Identification of common predisposing loci to hematopoietic cancers in four dog breeds

International audienceHistiocytic sarcoma (HS) is a rare but aggressive cancer in both humans and dogs. The spontaneous canine model, which has clinical, epidemiological, and histological similarities with human HS and specific breed predispositions, provides a unique opportunity to unravel the genetic basis of this cancer. In this study, we aimed to identify germline risk factors associated with the development of HS in canine-predisposed breeds. We used a methodology that combined several genome-wide association studies in a multi-breed and multi-cancer approach as well as targeted next-generation sequencing, and imputation We combined several dog breeds (Bernese mountain dogs, Rottweilers, flat-coated retrievers, and golden retrievers), and three hematopoietic cancers (HS, lymphoma, and mast cell tumor). Results showed that we not only refined the previously identified HS risk CDKN2A locus, but also identified new loci on canine chromosomes 2, 5, 14, and 20. Capture and targeted sequencing of specific loci suggested the existence of regulatory variants in non-coding regions and methylation mechanisms linked to risk haplotypes, which lead to strong cancer predisposition in specific dog breeds. We also showed that these canine cancer predisposing loci appeared to be due to the additive effect of several risk haplotypes involved in other hematopoietic cancers such as lymphoma or mast cell tumors as well. This illustrates the pleiotropic nature of these canine cancer loci as observed in human oncology, thereby reinforcing the interest of predisposed dog breeds to study cancer initiation and progression. Author summary Because of specific breed structures and artificial selection, pet dogs suffer from numerous genetic diseases, including cancers and represent a unique spontaneous model of human cancers. Here, we focused on histiocytic sarcoma (HS), a rare and highly aggressive cancer in humans. In this study, we have used spontaneous affected and unaffected dogs from three predisposed dog breeds to identify loci involved in HS predisposition. Through genetic analyses, we showed that these canine cancer predispositions are due to the additive effect of several risk haplotypes also involved in the predisposition of other hematopoietic cancers. The corresponding chromosomal regions in humans are involved in the predisposition of several cancers and are also associated with immune traits. This study demonstrates the pleiotropic nature of these canine cancer loci as observed in human oncology, thereby reinforcing the interest of predisposed dog breeds to study mechanisms involved in cancer initiation

Dietary emulsifiers from milk and soybean differently impact adiposity and inflammation in association with modulation of colonic goblet cells in high-fat fed mice

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Scalable Generation of Pre‐Vascularized and Functional Human Beige Adipose Organoids

International audienceObesity and type 2 diabetes are becoming a global sociobiomedical burden. Beige adipocytes are emerging as key inducible actors and putative relevant therapeutic targets for improving metabolic health. However, in vitro models of human beige adipose tissue are currently lacking and hinder research into this cell type and biotherapy development. Unlike traditional bottom-up engineering approaches that aim to generate building blocks, here a scalable system is proposed to generate pre-vascularized and functional human beige adipose tissue organoids using the human stromal vascular fraction of white adipose tissue as a source of adipose and endothelial progenitors. This engineered method uses a defined biomechanical and chemical environment using tumor growth factor β (TGFβ) pathway inhibition and specific gelatin methacryloyl (GelMA) embedding parameters to promote the self-organization of spheroids in GelMA hydrogel, facilitating beige adipogenesis and vascularization. The resulting vascularized organoids display key features of native beige adipose tissue including inducible Uncoupling Protein-1 (UCP1) expression, increased uncoupled mitochondrial respiration, and batokines secretion. The controlled assembly of spheroids allows to translate organoid morphogenesis to a macroscopic scale, generating vascularized centimeter-scale beige adipose micro-tissues. This approach represents a significant advancement in developing in vitro human beige adipose tissue models and facilitates broad applications ranging from basic research to biotherapies

Guillain-Barré Syndrome Associated With Zika Virus Infection in Martinique in 2016: A Prospective Study

International audienceBackground: Guillain-Barré syndrome (GBS) has been reported to be associated with Zika virus (ZIKV) infection in case reports and retrospective studies, mostly on the basis of serological tests, with the problematic cross-reacting antibodies of the Flavivirus genus. Some GBS cases do not exhibit a high level of diagnostic certainty. This prospective study aimed to describe the clinical profiles and the frequency of GBS associated with ZIKV during the ZIKV outbreak in Martinique in 2016.Methods: We recorded prospective data from GBS meeting levels 1 or 2 of diagnostic certainty for the Brighton Collaboration, with proof of recent ZIKV infection and negative screening for etiologies of GBS.Results: Of the sample of 34 patients with suspected GBS during the outbreak, 30 had a proven presence of GBS, and 23 had a recent ZIKV infection. The estimated GBS incidence rate ratio (2016 vs 2006-2015) was 4.52 (95% confidence interval, 2.80-7.64; P = .0001). Recent ZIKV infection was confirmed by urine reverse-transcription polymerase chain reaction (RT-PCR) analysis in 17 cases and by serology in 6 cases. Patients, 65% of whom were male, had a median age of 61 years (interquartile range, 56-71 years) and experienced severe GBS. Electrophysiological tests were consistent with the primary demyelinating form of the disease.Conclusions: ZIKV infection is usually benign, when symptomatic, but in countries at risk of ZIKV epidemics, adequate intensive care bed capacity is required for management of severe GBS cases. Arbovirus RNA detection by RT-PCR should be part of the management of GBS cases

Characteristics and outcomes ofCOVID-19 in hospitalized patients with and without diabetes

International audienceBackground Coronavirus disease 2019 (COVID-19) is a rapidly progressing pandemic, with four million confirmed cases and 280 000 deaths at the time of writing. Some studies have suggested that diabetes is associated with a greater risk of developing severe forms of COVID-19. The primary objective of the present study was to compare the clinical features and outcomes in hospitalized COVID-19 patients with vs without diabetes. Methods All consecutive adult patients admitted to Amiens University Hospital (Amiens, France) with confirmed COVID-19 up until April 21st, 2020, were included. The composite primary endpoint comprised admission to the intensive care unit (ICU) and death. Both components were also analysed separately in a logistic regression analysis and a Cox proportional hazards model. Results A total of 433 patients (median age: 72; 238 (55%) men; diabetes: 115 (26.6%)) were included. Most of the deaths occurred in non-ICU units and among older adults. Multivariate analyses showed that diabetes was associated neither with the primary endpoint (odds ratio (OR): 1.12; 95% confidence interval (CI): 0.66-1.90) nor with mortality (hazard ratio: 0.73; 95%CI: 0.40-1.34) but was associated with ICU admission (OR: 2.06; 95%CI 1.09-3.92,P= .027) and a longer length of hospital stay. Age was negatively associated with ICU admission and positively associated with death. Conclusions Diabetes was prevalent in a quarter of the patients hospitalized with COVID-19; it was associated with a greater risk of ICU admission but not with a significant elevation in mortality. Further investigation of the relationship between COVID-19 severity and diabetes is warranted

The association between body mass index class and coronavirus disease 2019 outcomes

International audienceBackground/Objectives A growing body of data suggests that obesity influences coronavirus disease 2019 (COVID-19). Our study's primary objective was to assess the association between body mass index (BMI) categories and critical forms of COVID-19. Subjects/Methods Data on consecutive adult patients hospitalized with laboratory-confirmed COVID-19 at Amiens University Hospital (Amiens, France) were extracted retrospectively. The association between BMI categories and the composite primary endpoint (admission to the intensive care unit or death) was probed in a logistic regression analysis. Results In total, 433 patients were included, and BMI data were available for 329: 20 were underweight (6.1%), 95 have a normal weight (28.9%), 90 were overweight (27.4%), and 124 were obese (37.7%). The BMI category was associated with the primary endpoint in the fully adjusted model; the odds ratio (OR) [95% confidence interval (CI)] for overweight and obesity were respectively 1.58 [0.77-3.24] and 2.58 [1.28-5.31]. The ORs [95% CI] for ICU admission were similar for overweight (3.16 [1.29-8.06]) and obesity (3.05 [1.25-7.82]) in the fully adjusted model. The unadjusted ORs for death were similar in all BMI categories while obesity only was associated with higher risk after adjustment. Conclusions Our results suggest that overweight (and not only obesity) is associated with ICU admission, but overweight is not associated with death