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Research into the analysis, physical properties and health effects of dietary fibre has continued steadily over the last 40–50 years. From the knowledge gained, countries have developed guidelines for their populations on the optimal amount of fibre to be consumed each day. Food composition tables from many countries now contain values for the dietary fibre content of foods, and, from these, combined with dietary surveys, population intakes have been determined. The present review assessed the uniformity of the analytical methods used, health claims permitted, recommendations and intakes, particularly from national surveys across Europe and around the world. It also assessed current knowledge on health effects of dietary fibre and related the impact of different fibre types on health. The overall intent was to be able to provide more detailed guidance on the types of fibre which should be consumed for good health, rather than simply a total intake figure, the current situation. Analysis of data indicated a fair degree of uniformity in the definition of dietary fibre, the method used for analysis, the recommended amount to be consumed and a growing literature on effects on digestive health and disease risk. However, national dietary survey data showed that intakes do not reach recommendations and very few countries provide guidance on the types of fibre that are preferable to achieve recommended intakes. Research gaps were identified and ideas suggested to provide information for more detailed advice to the public about specific food sources that should be consumed to achieve health benefits.

Background: Circulating tumor cells (CTCs) are biomarkers for non-invasively measuring the evolution of tumor genotypes during treatment and disease progression. Recent technical progress has made it possible to detect and characterize CTCs at the single-cell level in blood. Content: Most current methods are based on epithelial cell adhesion molecule (EpCAM) detection, but numerous studies have demonstrated that EpCAM is not a universal marker for CTC detection since it fails to detect both carcinoma cells that undergo epithelial-mesenchymal transition (EMT), and CTCs of mesenchymal origin. Moreover, EpCAM expression has been found in patients with benign diseases. A large proportion of the current studies and reviews about CTCs describe EpCAM based methods, but there are evidences that not all tumor cells can be detected using this marker. Here we describe the most recent EpCAM-independent methods for enriching, isolating and characterizing CTCs, based on physical and biological characteristics, and point out their main advantages and disadvantages.Summary: CTCs offer an opportunity to obtain key biological information required for the development of personalized medicine. However there is no universal marker of these cells. To strengthen the clinical utility of CTCs, it is important to improve existing technologies and develop new, non-EpCAM based systems to enrich and isolate CTCs.

Breastmilk is known to be very important for infants because it provides nutrients and immunological compounds. Among these compounds, human milk oligosaccharides (HMOs) represent the third most important component of breastmilk after lipids and lactose. Several experiments demonstrated the beneficial effects of these components on the microbiota, the immune system and epithelial barriers, which are three major biological systems. Indeed, HMOs induce bacterial colonization in the intestinal tract, which is beneficial for health. The gut bacteria can act directly and indirectly on the immune system by stimulating innate immunity and controlling inflammatory reactions and by inducing an adaptive immune response and a tolerogenic environment. In parallel, HMOs directly strengthen the intestinal epithelial barrier, protecting the host against pathogens. Here, we review the molecular mechanisms of HMOs in these different compartments and highlight their potential use as new therapeutic agents, especially in allergy prevention.

Non-alcoholic fatty liver disease (NAFLD) affects about 20–40% of the adult population in high-income countries and is now a leading indication for liver transplantation and can lead to hepatocellular carcinoma. The link between gut microbiota dysbiosis and NAFLD is now clearly established. Through analyses of the gut microbiota with shotgun metagenomics, we observe that compared to healthy controls, Adlercreutzia equolifaciens is depleted in patients with liver diseases such as NAFLD. Its abundance also decreases as the disease progresses and eventually disappears in the last stages indicating a strong association with disease severity. Moreover, we show that A. equolifaciens possesses anti-inflammatory properties, both in vitro and in vivo in a humanized mouse model of NAFLD. Therefore, our results demonstrate a link between NAFLD and the severity of liver disease and the presence of A. equolifaciens and its anti-inflammatory actions. Counterbalancing dysbiosis with this bacterium may be a promising live biotherapeutic strategy for liver diseases.

(1) Background: Gut microbiota-dependent Trimethylamine-N-oxide (TMAO) has been 5 reported to be strongly linked to renal function and to increased cardiovascular events in the 6 general population and in Chronic Kidney Disease (CKD) patients. Considering the lack of data 7 assessing renal handling of TMAO, we conducted this study to explore renal excretion and 8 mechanisms of accumulation of TMAO during CKD. (2) Methods: We prospectively measured 9 glomerular filtration rate (mGFR) with gold standard methods and plasma concentrations of 10 trimethylamine (TMA), TMAO, choline, betaine and carnitine by LC-MS/MS in 124 controls, CKD 11 and hemodialysis (HD) patients. Renal clearance of each metabolite was assessed in a subgroup of 12 32 patients. (3) Results: Plasma TMAO was inversely correlated with mGFR (r 2 =0.388, p<0.001), 13 confirming elevation of TMAO plasma levels in CKD. TMAO clearances were not significantly 14 different from mGFR, with a mean ± SD TMAO fractional excretion of 105 ± 32 %. This suggests a 15 complete renal excretion of TMAO by glomerular filtration with a negligible participation of 16 tubular secretion or reabsorption, during all stages of CKD. Moreover, TMAO was effectively 17 removed within 4 hours of hemodiafiltration, showing a higher fractional reduction value than that 18 of urea (84.9 ± 6.5 % vs 79.2 ± 5.7 %, p = 0.04). (5) Conclusions: This study reports a strong 19 correlation between plasma TMAO levels and mGFR, in CKD, that can be mainly related to a 20 decrease in TMAO glomerular filtration. Clearance data did not support a significant role for 21 tubular secretion in TMAO renal elimination. 22

Tumour heterogeneity refers to the fact that different tumour cells can show distinct morphological and phenotypic profiles, including cellular morphology, gene expression, metabolism, motility, proliferation, and metastatic potential. This phenomenon occurs both between tumours (inter-tumour heterogeneity) and within tumours (intra-tumour heterogeneity), and it is caused by genetic and non-genetic factors. The heterogeneity of cancer cells introduces significant challenges in using molecular prognostic markers as well as for classifying patients that might benefit from specific therapies. Thus, research efforts for characterizing heterogeneity would be useful for a better understanding of the causes and progression of disease. It has been suggested that the study of heterogeneity within Circulating Tumour Cells (CTCs) could also reflect the full spectrum of mutations of the disease more accurately than a single biopsy of a primary or metastatic tumour. In the last years many high throughput methodologies have raised for the study of heterogeneity at different levels (i.e.: RNA, DNA, protein, epigenetic events). The aim of the current review is to stress clinical implications of tumour heterogeneity, as well as current available methodologies for their study with a specific attention to those able to assess heterogeneity at the single cell level.

The intestinal microbiota plays an essential role in many diseases, such as obesity, irritable bowel disease (IBD), and cancer. This study aimed to characterize the faecal microbiota from early-stage breast cancer (BC) patients and healthy controls. Faeces from newly diagnosed breast cancer patients, mainly for an invasive carcinoma of no specific type (HR+ and HER2−), before any therapeutic treatment and healthy controls were collected for metabarcoding analyses. We show that the Shannon index, used as an index of diversity, was statistically lower in the BC group compared to that of controls. This work highlights a reduction of microbial diversity, a relative enrichment in Firmicutes, as well as a depletion in Bacteroidetes in patients diagnosed with early BC compared to those of healthy women. A tendency towards a decreased relative abundance of Odoribacter sp., Butyricimonas sp., and Coprococcus sp. was observed. This preliminary study suggests that breast cancer patients may differ from healthy subjects in their intestinal bacterial composition.

Background The efficacy and safety of tralokinumab, a fully human monoclonal antibody that specifically neutralizes interleukin-13, plus topical corticosteroids (TCS) as needed were evaluated over 32 weeks in the phase III ECZTRA 3 trial. Significantly more tralokinumab- versus placebo-treated patients achieved the primary endpoints of Investigator’s Global Assessment (IGA) score of 0/1 and 75% improvement in Eczema Area and Severity Index (EASI-75) and all confirmatory endpoints at Week 16. Objective This post hoc analysis investigated the impact of tralokinumab plus TCS on atopic dermatitis (AD) severity, symptoms, and health-related quality of life (QoL) over the entire 32-week treatment period of ECZTRA 3, including all patients initiated on tralokinumab irrespective of the response achieved at Week 16. Methods Patients were randomized 2:1 to receive subcutaneous tralokinumab 300 mg or placebo every 2 weeks (q2w) with TCS as needed for an initial 16 weeks. At Week 16, patients who achieved the clinical response criteria (IGA 0/1 and/or EASI-75) with tralokinumab were re-randomized 1:1 to tralokinumab q2w or every 4 weeks (q4w), with TCS as needed, for another 16 weeks. Patients not achieving the clinical response criteria with tralokinumab received tralokinumab q2w plus TCS from Week 16. All patients randomized to tralokinumab in the initial treatment period were pooled for this analysis, irrespective of response at Week 16 or dosing regimen beyond Week 16. Results Continued tralokinumab (q2w, N = 164; q4w, N = 69) plus TCS treatment provided progressive improvements from Week 16 onwards in AD signs, with 70.2% (177/252) of patients achieving EASI-75 and 50.4% (127/252) achieving EASI-90 at Week 32. Improvements in patient-reported outcomes were observed within the first few weeks of tralokinumab q2w plus TCS treatment and were sustained throughout the 32-week period. At Week 32, patients initiated on tralokinumab q2w plus TCS achieved a relative improvement versus baseline of 70.8% (standard error (SE), 2.4) in eczema-related sleep interference numeric rating scale (NRS) and 66.8% (SE, 3.1) in Dermatology Life Quality Index (DLQI). Mean TCS use during Weeks 16–32 ranged from 9.2 to 13.6 g (SE, 1.2–2.0) q2w. Most patients (89.9% (222/247)) initiated on tralokinumab q2w plus TCS achieved a meaningful improvement in at least one of the three disease domains, including AD signs (EASI-50), symptoms (pruritus NRS improvement ≥ 3), and QoL (DLQI improvement ≥ 4) at Week 16. Of patients initiated on tralokinumab q2w plus TCS, 53.4% (132/247) achieved a clinically meaningful improvement in all three domains at Week 16 (vs. placebo, 28.5% (35/123); p  < 0.001). Conclusions Continued tralokinumab treatment plus TCS as needed provides progressive and sustained improvements in AD signs, symptoms, and health-related QoL over 32 weeks. Clinical trial registration NCT03363854; study start date: 22 February 2018; primary completion date: 8 March 2019; study completion date: 26 September 2019. Infographic D4wLg_z9a1xaBhX7Cv9x3S Video abstract: What is the impact of tralokinumab plus topical corticosteroids in adults with moderate-to-severe atopic dermatitis over 32 weeks? (MP4 216,988 KB) Plain Language Summary: Treatment with tralokinumab plus topical corticosteroids provided continued improvements over a 32-week study period Atopic dermatitis (AD) is a chronic inflammatory disease that causes excessively dry and itchy skin that can negatively impact sleep and overall quality of life for patients. Topical corticosteroids (TCS) are the most common medication used for AD, but they are not able to control the most severe cases. Tralokinumab is a treatment injected under the skin that targets an immune messenger protein called interleukin 13, which plays a key role in driving the signs and symptoms of AD. The ECZTRA 3 clinical trial, funded by LEO Pharma, compared the use of TCS as needed with either tralokinumab or placebo in over 350 adult patients with moderate-to-severe AD over a 32-week period. After 16 weeks, more patients taking tralokinumab plus TCS had clear or almost clear skin compared with patients taking placebo plus TCS. Patients taking tralokinumab also used less TCS than patients taking placebo. In new analyses presented here, we found that the proportion of patients with clear or almost clear skin continued to increase with on-going treatment from Week 16 to Week 32. Tralokinumab plus TCS treatment also led to clinically meaningful improvements in outcomes important to patients, including itch, sleep, and quality of life. Improvements occurred early, within the first few weeks of therapy, and lasted through Week 32. Our assessment of multiple outcomes over time clearly demonstrates the positive impact of tralokinumab on different aspects of AD.

This study aimed to identify the risk factors for placenta accreta spectrum (PAS) in women who had at least one previous cesarean delivery and a placenta previa or low-lying. The PACCRETA prospective population-based study took place in 12 regional perinatal networks from 2013 through 2015. All women with one or more prior cesareans and a placenta previa or low lying were included. Placenta accreta spectrum (PAS) was diagnosed at delivery according to standardized clinical and histological criteria. Of the 520,114 deliveries, 396 fulfilled inclusion criteria; 108 were classified with PAS at delivery. Combining the number of prior cesareans and the placental location yielded a rate ranging from 5% for one prior cesarean combined with a posterior low-lying placenta to 63% for three or more prior cesareans combined with placenta previa. The factors independently associated with PAS disorders were BMI ≥ 30, previous uterine surgery, previous postpartum hemorrhage, a higher number of prior cesareans, and a placenta previa. Finally, in this high-risk population, the rate of PAS disorders varies greatly, not only with the number of prior cesareans but also with the exact placental location and some of the women's individual characteristics. Risk stratification is thus possible in this population.

BackgroundAn increased risk for bronchopulmonary dysplasia (BPD) exists when moderate-to-large patent ductus arteriosus shunts (hsPDA) persist beyond 14 days.GoalTo examine the interaction between prolonged exposures to tracheal ventilation (≥10 days) and hsPDA on the incidence of BPD in infants <28 weeks gestation.Study DesignPredefined definitions of prolonged ventilation (≥10 days), hsPDA (≥14 days), and BPD (room air challenge test at 36 weeks) were used to analyze deidentified data from the multicenter TRIOCAPI RCT in a secondary analysis of the trial.ResultsAmong 307 infants who survived >14 days, 41 died before 36 weeks. Among survivors, 93/266 had BPD. The association between BPD and hsPDA depended on the length of intubation. In multivariable analyses, prolonged hsPDA shunts were associated with increased BPD (odds ratio (OR) (95% confidence interval (CI)) = 3.00 (1.58–5.71)) when infants required intubation for ≥10 days. In contrast, there was no significant association between hsPDA exposure and BPD when infants were intubated <10 days (OR (95% CI) = 1.49 (0.98–2.26)). A similar relationship between prolonged hsPDA and length of intubation was found for BPD/death (n = 307): infants intubated ≥10 days: OR (95% CI) = 2.41 (1.47–3.95)); infants intubated <10 days: OR (95% CI) = 1.37 (0.86–2.19)).ConclusionsModerate-to-large PDAs were associated with increased risks of BPD and BPD/death—but only when infants required intubation ≥10 days.ImpactInfants with a moderate-to-large hsPDA that persist beyond 14 days are only at risk for developing BPD if they also receive prolonged tracheal ventilation for ≥10 days.Infants who receive less ventilatory support (intubation for <10 days) have the same incidence of BPD whether the ductus closes shortly after birth or whether it persists as a moderate-to-large shunt for several weeks.Early PDA closure may be unnecessary in infants who require short durations of intubation since the PDA does not seem to alter the incidence of BPD in infants who require intubation for <10 days.