Solid food introduction may create anxiety for parents of children with phenylketonuria (PKU) due to the burden associated with protein substitute (PS) administration and natural protein restriction. In a longitudinal, prospective study, 20 mothers of children with PKU and 20 non-PKU control mothers completed 4 questionnaires (mealtime emotions, feed-time, Beck’s anxiety inventory and the coping health inventory for parents), examining parent/child mealtime emotions, anxiety, stress and coping strategies at child ages: weaning start, 8 months (m), 12 m, 15 m, 18 m and 24 m. Overall, mothers of children with PKU cope well with solid food introduction when applying a low-phenylalanine diet, with comparable low levels of stress and anxiety reported in both PKU and non-PKU groups. However, mothers of children with PKU reported peak scores in anxiety for emotive/cognitive symptoms at a child age of 15 m, and higher use of coping strategies at 15 m and 24 m (p < 0.05) of age. Generally, there was a trend that maternal anxiety regarding child rejection of PS increased with time, peaking between 12–24 m. In PKU, a child age of 12–18 m is identified as a key period when mothers feel most anxious/stressed with feeding, coinciding with raised blood phenylalanine levels probably associated with teething, illness and developing independence. Health professionals should be conscious of this vulnerable period and be prepared to offer more directional support as required. Full article

As a result of increased consumer awareness, demand for healthier food products is increasing day by day. Consumers seek healthier versions of food products which they relate to reduced presence of unhealthy components or increased presence of healthy ones. As a result, the food industry has not only increased the variety of products available but also uses nutritional claims to signal the presence of more substances. As an average consumer at the supermarket devotes just a few seconds to selecting each product, they are only able or willing to process that information that immediately attracts their attention or that is felt to be more important to them. This paper analyses how consumers rank different nutritional claims for two processed cereal products. Five claims were chosen to reflect the current market landscape of availability, and that relates to both “healthy” (i.e., fiber) and “unhealthy” (i.e., fat) substances. We use a direct ranking preference method with data from a survey conducted with consumers in a Spanish region in 2017. Results show that the ranking of claims differs between the two products (biscuits and pastries) and across consumers. However, consumers prefer those that show reduced presence of unhealthy substances above those that highlight the presence of healthy ones. Therefore, policy to maximize the impact of nutritional labelling should be product-specific. Full article

Fucosylated chondroitin sulfate (fCS) is a glycosaminoglycan found up to now exclusively in the body wall of sea cucumbers. It shows several interesting activities, with the anticoagulant and antithrombotic as the most attractive ones. Its different mechanism of action on the blood coagulation cascade with respect to heparin and the retention of its activity by oral administration make fCS a very promising anticoagulant drug candidate for heparin replacement. Nonetheless, its typically heterogeneous structure, the detection of some adverse effects and the preference for new drugs not sourced from animal tissues, explain how mandatory is to open an access to safer and less heterogeneous non-natural fCS species. Here we contribute to this aim by investigating a suitable chemical strategy to obtain a regioisomer of the natural fCS polysaccharide, with sulfated l-fucosyl branches placed at position O-6 of N-acetyl-d-galactosamine (GalNAc) units instead of O-3 of d-glucuronic acid (GlcA) ones, as in natural fCSs. This strategy is based on the structural modification of a microbial sourced chondroitin polysaccharide by regioselective insertion of fucosyl branches and sulfate groups on its polymeric structure. A preliminary in vitro evaluation of the anticoagulant activity of three of such semi-synthetic fCS analogues is also reported. Full article

The occurrence of optic pathway gliomas (OPGs) in children with neurofibromatosis type 1 (NF1) still raises many questions regarding screening and surveillance because of the lack of robust prognostic factors. Recent studies of an overall cohort of 381 patients have suggested that the genotype may be the main determinant of the development of OPG, with the risk being higher in patients harbouring NF1 mutations in the 5’ tertile and the cysteine/serine-rich domain. In an attempt to confirm this hypothesis, we used strict criteria to select a large independent cohort of 309 NF1 patients with defined constitutional NF1 mutations and appropriate brain images (255 directly enrolled and 54 as a result of a literature search). One hundred and thirty-two patients had OPG and 177 did not. The association of the position (tertiles and functional domains) and type of NF1 mutation with the development of OPG was analysed using the χ2 test and Fisher’s exact probability test; odds ratios (ORs) with 95% confidence intervals were calculated, and Bonferroni’s correction for multiple comparisons was applied; multiple logistic regression was also used to study genotype–phenotype associations further. Our findings show no significant correlation between the site/type of NF1 mutation and the risk of OPG, and thus do not support the hypothesis that certain constitutional mutations provide prognostic information in this regard. In addition, we combined our cohort with a previously described cohort of 381 patients for a total of 690 patients and statistically re-analysed the results. The re-analysis confirmed that there were no correlations between the site (tertile and domain) and the risk of OPG, thus further strengthening our conclusions. Full article

Our special series on Cardiac Rehabilitation outlined the importance of routine physical activity and/or exercise participation in the primary and secondary prevention of cardiovascular disease and many other chronic medical conditions. The evidence is overwhelming, demonstrating that nearly everyone can benefit from becoming more physically active. This messaging has been widely disseminated at regional, national, and international levels. Often, this messaging highlights a physical inactivity crisis and the health perils of not engaging in sufficient amounts of physical activity. This deficits-based messaging often includes generic threshold-based recommendations stating that health benefits can only be accrued with specific volumes or intensities of physical activity. In this Editorial, we argue that the current generic and deficits-based messaging misses a great opportunity to focus on the positive and to facilitate hope and real change at the individual, community, and population levels. We advocate a strengths-based approach to health and wellness promotion that focuses on the innate strengths of individuals, families, and communities to enable self-empowerment and self-determination related to health and wellness. By taking a strengths-based approach, we can build hope, promoting the positive aspects of routine physical activity and exercise participation and providing a greater opportunity to enhance health and wellbeing for everyone. Full article

Lysyl oxidase (LOX) proteins comprise a family of five copper-dependent enzymes (LOX and four LOX-like isoenzymes (LOXL1–4)) critical for extracellular matrix (ECM) homeostasis and remodeling. The primary role of LOX enzymes is to oxidize lysyl and hydroxylysyl residues from collagen and elastin chains into highly reactive aldehydes, which spontaneously react with surrounding amino groups and other aldehydes to form inter- and intra-catenary covalent cross-linkages. Therefore, they are essential for the synthesis of a mature ECM and assure matrix integrity. ECM modulates cellular phenotype and function, and strikingly influences the mechanical properties of tissues. This explains the critical role of these enzymes in tissue homeostasis, and in tissue repair and remodeling. Cardiac ECM is mainly composed of fibrillar collagens which form a complex network that provides structural and biochemical support to cardiac cells and regulates cell signaling pathways. It is now becoming apparent that cardiac performance is affected by the structure and composition of the ECM and that any disturbance of the ECM contributes to cardiac disease progression. This review article compiles the major findings on the contribution of the LOX family to the development and progression of myocardial disorders. Full article

A low fermentable oligosaccharide, disaccharide, monosaccharide, and polyol (FODMAP) diet has been recommended for irritable bowel syndrome (IBS) patients. This study compared the efficacy of two types of dietary advice: (1) brief advice on a commonly recommended diet (BRD), and (2) structural individual low-FODMAP dietary advice (SILFD). Patients with moderate-to-severe IBS were randomized to BRD or SILFD groups. Gastrointestinal symptoms, 7-day food diaries, and post-prandial breath samples were evaluated. The SILFD included (1) identifying high-FODMAP items from the diary, (2) replacing high-FODMAP items with low-FODMAP ones by choosing from the provided menu. The BRD included reducing traditionally recognized foods that cause bloating/abdominal pain and avoidance of large meals. Responders were defined as those experiencing a ≥30% decrease in the average of daily worst abdominal pain/discomfort after 4 weeks. Sixty-two patients (47 F, age 51 ± 14 years), BRD (n = 32) or SILFD (n = 30), completed the studies. Eighteen (60%) patients in SILFD vs. 9 (28%) in the BRD group fulfilled responder criteria (p = 0.001). Global IBS symptom severity significantly improved and the number of high-FODMAP items consumed was significantly decreased after SILFD compared to BRD. Post-prandial hydrogen (H₂) breath production after SILFD was significantly lower than was seen after BRD (p < 0.001). SILFD was more effective than BRD. This advice method significantly reduced FODMAP intake, improved IBS symptoms, and lowered intestinal H₂ production. Full article

MicroRNAs (miRs) significantly contribute to the regulation of gene expression, by virtue of their ability to interact with a broad, yet specific set of target genes. MiRs are produced and released by almost every cell type and play an important role in horizontal gene regulation in the tumor microenvironment (TME). In the TME, both tumor and stroma cells cross-communicate via diverse factors including miRs, which are taking central stage as a therapeutic target of anti-tumor therapy. One of the immune escape strategies adopted by tumor cells is to release miRs as a Trojan horse to hijack circulating or tumor-localized monocytes/macrophages to tune them for pro-tumoral functions. On the other hand, macrophage-derived miRs exert anti-tumor functions. The transfer of miRs from host to recipient cells depends on the supramolecular structure and composition of miR carriers, which determine the distinct uptake mechanism by recipient cells. In this review, we provide a recent update on the miR-mediated crosstalk between tumor cells and macrophages and their mode of uptake in the TME. Full article

Offshore wind turbine monopile foundations are subjected to complex wind, wave, and flow coupling effects, which result in seabed scouring around the monopile. The consequent scour pits threaten the reliability, safety, and load-carrying capacity of the monopile. In order to develop a cost-effective measure to mitigate such an issue, a new countermeasure device, named “fishnet”, is studied in this paper using a combined approach of numerical simulations and experimental tests. In the research, the size of the fishnet, diameter of the fishnet thread, and the installation height of the fishnet were optimized in order to achieve the best protection to the monopile foundation. In the paper, both numerical simulations and laboratory tests proved the effectiveness of the proposed “fishnet” in reducing the scour around the wind turbine monopile foundations. Moreover, its contribution to erosion reduction can be further enhanced via optimization. It was found that, after optimization, the maximum shear force on the seabed could be reduced by 14% in the numerical study, and the maximum depth of the scour pit could be reduced by 38.2% in laboratory tests. Full article

Nowadays, the analysis of the multi-components in Chinese patent medicine prescriptions is being paid more attention. Therefore, in this study for the first time, a simple, rapid ultrahigh performance liquid chromatography–electrospray ionization tandem mass spectrometry (UHPLC-ESI-MS/MS) method was established for simultaneous determination of 18 active compounds in a Chinese patent medicine of Hu Gan tablets (HGT) from different pharmaceutical factories in China. This task has met great emerging challenges from not only structural complexities and similarities but also co-occurrence of water-soluble and fat-soluble components in HGT. UPLC-ESI-MS/MS was put forward to solve the problems. It was operated in both positive and negative mode using multiple reaction monitoring (MRM). The mobile phase was 0.1% formic acid in water (A) −0.1% formic acid in acetonitrile (B) with linear gradient elution at a flow rate of 0.2 mL/min, run for a total of 12.0 min. The optimized method used provided short analysis time and good linearity (R² > 0.99), and intra- and inter-day precision (relative standard deviation (RSD) < 4.00%) with good accuracy (94.89–110.03%) and recovery (70.00–126.09%). The results indicate the method could be practically used for quality guarantee of HGT and might also be useful for further studies. Full article

Transforming growth factor-β (TGFβ) has both tumor-suppressive and tumor-promoting effects in breast cancer. These functions are partly mediated through Smads, intracellular transcriptional effectors of TGFβ. Smads form complexes with other DNA-binding transcription factors to elicit cell-type-dependent responses. Previously, we found that the collagen invasion and migration of pre-malignant breast cancer cells in response to TGFβ and epidermal growth factor (EGF) critically depend on multiple Jun and Fos components of the activator protein (AP)-1 transcription factor complex. Here we report that the same process is negatively regulated by Jun N-terminal kinase (JNK)-dependent cJun phosphorylation. This was demonstrated by analysis of phospho-deficient, phospho-mimicking, and dimer-specific cJun mutants, and experiments employing a mutant version of the phosphatase MKP1 that specifically inhibits JNK. Hyper-phosphorylation of cJun by JNK strongly inhibited its ability to induce several Jun/Fos-regulated genes and to promote migration and invasion. These results show that MEK-AP-1 and JNK-phospho-cJun exhibit distinct pro- and anti-invasive functions, respectively, through differential regulation of Smad- and AP-1-dependent TGFβ target genes. Our findings are of importance for personalized cancer therapy, such as for patients suffering from specific types of breast tumors with activated EGF receptor-Ras or inactivated JNK pathways. Full article

Composite ZrB₂–MoSi₂ coating modified by Y₂O₃ and Al was prepared by a new multi-chamber detonation accelerator (MCDS) on carbon/carbon composites. Postdeposition heat treatment of the samples at 1500 °C for 1 and 6 h was carried out in air. The effect of heat treatment on the microstructure and phase composition of the ZrB₂–MoSi₂ coating was investigated by scanning electron microscopy and X-ray diffraction phase analysis. The as-sprayed coating presented as a dense lamellar structure, composed of m-ZrO₂, t-ZrO₂, some hexagonal ZrB₂, and cubic Al phases. The m-ZrO₂, c-ZrO₂, and h-(α-Al₂O₃) formed at 1500 °C. The coatings after heat treatment (1 and 6 h) exhibited a structure without cracks. The porosity (~1%) of the coating did not change after heat treatment. Thin, continuous, silica-rich film covered the surfaces of ZrO₂ and Al₂O₃ particles, and could have played a role during heat treatment by acting as a grain lubricant for particle rearrangement. Full article