Effects of Dietary Plant Sterols and Stanol Esters with Low- and High-Fat Diets in Chronic and Acute Models for Experimental Colitis

In this study, we evaluated the effects of dietary plant sterols and stanols as their fatty acid esters on the development of experimental colitis. The effects were studied both in high- and low-fat diet conditions in two models, one acute and another chronic model of experimental colitis that resembles gene expression in human inflammatory bowel disease (IBD). In the first experiments in the high fat diet (HFD), we did not observe a beneficial effect of the addition of plant sterols and stanols on the development of acute dextran sulphate sodium (DSS) colitis. In the chronic CD4CD45RB T cell transfer colitis model, we mainly observed an effect of the presence of high fat on the development of colitis. In this HFD condition, the presence of plant sterol or stanol did not result in any additional effect. In the second experiments with low fat, we could clearly observe a beneficial effect of the addition of plant sterols on colitis parameters in the T cell transfer model, but not in the DSS model. This positive effect was related to the gender of the mice and on Treg presence in the colon. This suggests that especially dietary plant sterol esters may improve intestinal inflammation in a T cell dependent manner.     

Design of melt-recyclable poly(ε-caprolactone)-based supramolecular shape-memory nanocomposites

A novel poly(epsilon-caprolactone) (PCL) supramolecular network exhibiting shape-memory behavior was successfully constructed with pendant UPy units that are highly able to dimerize. The dynamic network was obtained by a simple and versatile strategy consisting of chain-extension reaction between α,ω-dihydroxyoligoPCL and hydroxylated UPy units in the presence of hexamethylene diisocyanate as a coupling agent and further intermolecular dimerization of the UPy along the polyurethane backbone. ¹H NMR analyses confirmed the dynamic features of the system, and DMTA in tensile mode was investigated to assess the SMP properties. Recyclability was also assessed by taking advantage of these supramolecular networks. Further addition of cellulose nanocrystals into the polymer network enabled adjustment of the extent of the net-points and therefore the SMP features. As confirmed by dispersion tests in solution and SEM observations, these bio-based nanofillers were homogeneously distributed in the network via supramolecular interaction between the hydroxyl groups present on their surface and UPy moieties along the polyurethane backbone. Thus, the here developed nanomaterials might reveal applicability in areas where a combination of SMP and biocompatibility is needed.

Novel melt-recyclable poly(ε-caprolactone)/cellulose nanocrystals supramolecular nanocomposite networks with shape-memory behavior have been successfully constructed by playing with UPy chemistry.     

Oral antineoplastic agents: how do we care about adherence?

AimsOral therapies, including hormone‐based or targeted therapies, have recently taken an increasing place in cancer treatment. In this context, a state of the art of the available studies dealing with the adherence of adult patients to oral anticancer treatment is warranted. The purpose of this review is to address (i) the association between assessment methods and measured adherence, (ii) the putative factors related to adherence and (iii) new ways of improving adherence to oral cancer therapies.MethodsWe conducted a literature‐based narrative review of studies obtained from Pubmed using medical subject heading terms and free‐text terms combining concepts related to oral anticancer medication and adherence.ResultsThe analysis is based on 48 studies published since 1990, mostly assessing hormone‐based therapy in breast cancer and targeted therapies in chronic myeloid leukaemia. Various methods of adherence were reported including self‐report, medication measurement or combinations of methods. Adherence rates were found to vary from 14% to 100%. Beside patient related‐factors, adherence rate discrepancies were found to be dependent on the method used. Furthermore, there was no consensual definition of adherence even regarding the same methods, some of them tolerating a period of interruption during the treatment period. Finally, several studies addressing persistence found a progressive decrease in adherence with time.ConclusionAdherence to novel oral therapies is a major issue and further research is warranted to standardize adherence assessment in clinical studies better and to define better the most appropriate approaches to improve long term adherence in oncology practice.     

Do polymorphisms of apoB, LPL or apoE affect the hypocholesterolemic response to weight loss?

To assess whether there is a differential hypocholesterolemic response to weight loss for subjects carrying polymorphisms of the apolipoprotein B and other genes. A before and after comparison of lipid parameters following a calorie controlled diet for an intervention period of 12 weeks. A lipid clinic based in a large teaching hospital. The difference in slope coefficients relating the percentage change in lipid parameters to the change in body weight (adjusted for age, gender and initial body mass index (BMI)), for genotype subgroups defined by polymorphisms of the 5'VNTR apoB gene, two mutations of the LPL gene and ApoE. One hundred and forty six subjects completed the intervention diet. While, on average, the intervention was successful (mean weight loss 3.9%), there was no statistically significant difference in the slope coefficients relating lipid change to weight loss for most of the genotypes tested. The slope difference for long versus short 5'VNTR alleles of the apoB gene was 0.445 (-1.307, 2.198) for apolipoprotein B and -0. 104 (-1.486, 1.278) for total cholesterol. However, subjects carrying at least one varepsilon4 allele were significantly hypo-responsive to weight loss, difference in slope coefficients -1.087 (-2.09, -0.084) and -1.320 (-2.589, 0.051) for total cholesterol and apoB, respectively. Although, this study is one of the largest of its kind, it has not replicated the findings of other smaller studies. These findings do not provide support for the use of genotype-targeted dietary advice in routine practice.     

Heart failure and diabetes mellitus: epidemiology and management of an alarming association

Diabetes mellitus is a growing epidemic with a prevalence among patients with heart failure (HF) approaching 30%. Diabetes worsens the prognosis of HF, and the pathophysiology is complex and multifactorial. Early detection of subtle alterations in cardiac function by modern tools, such as Doppler echocardiography or brain natriuretic peptide dosage, is thus important in these patients. All drugs known to be effective in HF with systolic dysfunction are also effective in patients with diabetes. Angiotensin-converting enzyme inhibitors and angiotensin II receptor antagonists also seem particularly useful. Overall, however, little is known about the treatment of diabetic patients with HF, especially in case of preserved systolic function. Ongoing and future trials should help to determine the best treatment for these patients with or without associated diabetes. This review assesses the relationships between diabetes mellitus and HF and discusses the various medical strategies.     

SOD2 genetic polymorphism (rs4880) has no impact on 6‐month response to antidepressant treatment and inflammatory biomarkers in depressed patients

Two thirds of patients suffering from a major depressive episode (MDE) do not reach a complete response with antidepressant drugs. This lack of response is due to several factors, including genetic determinants. Since major depressive disorder is associated with inflammatory and oxidative stress abnormalities, the metabolism of superoxide anions might be involved in non‐response to antidepressant drugs. Superoxide anions are metabolized by manganese‐dependent superoxide dismutase (SOD2) in the mitochondria. A functional genetic polymorphism (SOD2, rs4880), responsible of a 40% reduction in enzyme activity, is associated with anti‐inflammatory response of rosuvastatin. We investigated the association of ala‐allele of SOD2 rs4880 and both antidepressant efficacy and inflammatory parameters in patients treated for a MDE with antidepressant drugs. The Hamilton Depression Rating Scale (HDRS) score and levels of plasma CRP and inflammatory cytokines were assessed at baseline, one month (M1), 3 months (M3) and 6 months (M6) after antidepressant treatment. They were compared according to SOD2 genetic polymorphism. Of the 484 patients studied, 361 (74.6%) carried the ala‐allele (Ala group), 123 (25.4%) of them had Val/Val genotype (Val/Val group). No significant difference was observed between the Ala and Val/Val groups neither for baseline clinical characteristics, nor for HDRS scores, response/remission rates, plasma CRP and cytokine levels throughout the study. The rs4880 SOD2 genetic polymorphism was not associated with the clinical response and cytokines levels after antidepressant treatment. These data suggest that SOD2 is not a major genetic determinant of antidepressant response. Other genes of the oxidative stress pathways should be explored in further studies.     

Infection Due to Mycobacterium thermoresistibile: a Case Associated with an Orthopedic Device

Mycobacterium thermoresistibile is a rapidly growing environmental nontuberculous mycobacterium, seldom reported in human infections. Here, we describe a rare case of tibial-nail-related osteomyelitis due to Mycobacterium thermoresistibile. We also review the literature about the infections caused by this pathogen.     

SARS-CoV-2 infection inducing severe flare up of Deficiency of Interleukin Thirty-six (IL-36) Receptor Antagonist (DITRA) resulting from a mutation invalidating the activating cleavage site of the IL-36 receptor antagonist

Journal of Clinical Immunology -