Update on the role of modified release mesalamine in the management of ulcerative colitis and Crohn’s disease

5-aminosalicyclates (5-ASA) remain a key first-line therapy for patients with ulcerative colitis (UC). A range of 5-ASA preparations is available and Eudragit-S® coated modified release formulations of mesalamine, such as Asacol®, remain among the most popular choices. We here review the current understanding of the mechanism of action of 5-ASA in inflammatory bowel disease. We evaluate evidence supporting the efficacy and safety of modified release mesalamine for both induction and remission maintenance in UC, including a review of the data from the recent ASCEND studies. We also examine the controversial issue of the role of mesalamine in treatment of Crohn’s disease (CD) and highlight data supporting its use following surgically induced remission of CD. Evidence supporting the use of mesalamine as prophylaxis for colorectal cancer and dysplasia will be considered. Finally, recent developments in our understanding of how to use modified release mesalamine in a safe and cost-effective manner are evaluated, including discussion of the importance of studying patient non-adherence as a key component of future studies in this area

Minimum requirements for feedback enhanced force sensing

The problem of estimating an unknown force driving a linear oscillator is revisited. When using linear measurement, feedback is often cited as a mechanism to enhance bandwidth or sensitivity. We show that as long as the oscillator dynamics are known, there exists a real-time estimation strategy that reproduces the same measurement record as any arbitrary feedback protocol. Consequently some form of nonlinearity is required to gain any advantage beyond estimation alone. This result holds true in both quantum and classical systems, with non-stationary forces and feedback, and in the general case of non-Gaussian and correlated noise. Recently, feedback enhanced incoherent force sensing has been demonstrated [Nat. Nano. \textbf{7}, 509 (2012)], with the enhancement attributed to a feedback induced modification of the mechanical susceptibility. As a proof-of-principle we experimentally reproduce this result through straightforward filtering.Comment: 5 pages + 2 pages of Supplementary Informatio

Healthy Outside-Healthy Inside: The Human Health & Well-being Benefits of Alberta\u27s Protected Areas - towards a benefits-based management agenda

This report details the results of an empirical study that examined perceived health and well-being motives and benefits among visitors to a sample of Alberta’s parks and protected areas. The study revealed several major findings with important policy and management implications. First, the human health and well-being benefits that the visitors expected to receive from visits were perceived to be a major personal motivation in the choice to visit Alberta protected areas. The most important motivation factors identified by respondents were psychological and emotional well-being (89.1% of visitors ranked this important), social well-being (88.3%), physical well-being (80.3%), and environmental well-being (79.4%). Second, the perceived benefits that visitors received from their protected areas experiences were substantial. The most frequently reported improvements were related to psychological and emotional (90.5%), social (85%), and physical well-being (77.6%). Interestingly, women perceived greater benefits than men associated with their visit, especially with respect to spiritual, social, and psychological and emotional well-being. Research findings substantiate the need for park agencies to better understand the motivations of visitors representing different social and population subgroups (e.g., youth, elderly, couples, etc.) in order to inform and develop policies and visitor experience programs in support of health and well-being related pursuits. Important policy and management implications for both park managers and health care professionals are highlighted

Perceived time, frequency, and intensity of engagement and older masters athletes' subjective experiences

Masters athletes are a unique group of older adults whose experiences may provide valuable insights into the role of sport for successful aging. The purpose of this study was to explore whether masters athletes' social and psychological experiences vary with their time, frequency, and perceived exertion in training and competition. Semi-structured interviews were conducted with 40 men and women older masters athletes, aged 50–79 years (M = 66), who were active at the competitive level across a variety of sports (e.g., volleyball, curling, rowing, dragon boating, running, swimming, and basketball) at the time of the study. Results indicate that all participants experienced social and psychological benefits from engaging in masters sport. Only the high-frequency engagement subgroup (participating five to seven times per week in training and/or competition) reported social downsides, in terms of missing time with family and friends outside of masters sport. However, some participants described the positive family support (e.g., spouse who endorses sport participation) that overrides some of the social costs. These findings have implications for realizing positive experiences with minimal engagement in masters sport, yet an apparent threshold of participation beyond which negative social consequences may be experienced. This is an important consideration for the design and promotion of sport for older adults

"Older, faster, stronger": the multiple benefits of masters sport participation

While masters sport aligns with the holistic concept of active aging, related research has focused predominantly on the physical domain, and less is known about the psychological, cognitive, and social benefits of older adults' participation. This study examined, in combination, the perceived psychological, social, cognitive, and physical benefits of training and competing as a masters athlete, while considering age and gender differences. Forty masters athletes residing in Canada were interviewed (21 men and 19 women; 15 who were 50-64 years and 25 who were 65-79 years), representing 15 different sports. Interviews were coded both deductively and inductively, revealing several subthemes of benefits for the broader perceived psychological, social, cognitive, and physical benefits, with few but notable differences between women and men, and those younger than 65 years and those 65+ years. Our findings provide new insights into the positive experiences of active aging associated with high levels of physical activity among older adults, such as greater self-confidence, especially for women, comradery, and feeling mentally sharper, especially for the older age group

Multiscale structural control of linked metal–organic polyhedra gel by aging-induced linkage-reorganization

Assembly of permanently porous metal–organic polyhedra/cages (MOPs) with bifunctional linkers leads to soft supramolecular networks featuring both porosity and processability. However, the amorphous nature of such soft materials complicates their characterization and thus limits rational structural control. Here we demonstrate that aging is an effective strategy to control the hierarchical network of supramolecular gels, which are assembled from organic ligands as linkers and MOPs as junctions. Normally, the initial gel formation by rapid gelation leads to a kinetically trapped structure with low controllability. Through a controlled post-synthetic aging process, we show that it is possible to tune the network of the linked MOP gel over multiple length scales. This process allows control on the molecular-scale rearrangement of interlinking MOPs, mesoscale fusion of colloidal particles and macroscale densification of the whole colloidal network. In this work we elucidate the relationships between the gel properties, such as porosity and rheology, and their hierarchical structures, which suggest that porosity measurement of the dried gels can be used as a powerful tool to characterize the microscale structural transition of their corresponding gels. This aging strategy can be applied in other supramolecular polymer systems particularly containing kinetically controlled structures and shows an opportunity to engineer the structure and the permanent porosity of amorphous materials for further applications

I-CARE, a European prospective cohort study assessing safety and effectiveness of biologics in inflammatory bowel disease

There is a need to evaluate the benefit-risk ratio of current therapies in inflammatory bowel disease (IBD) patients to provide the best quality of care. The primary objective of I-CARE was to assess prospectively safety concerns in IBD, with specific focus on the risk of cancer/lymphoma and serious infections in patients treated with for anti-tumor necrosis factor and other biologics monotherapy as well as in combination with immunomodulators.I-CARE was designed as a European prospective longitudinal observational multicenter cohort study, to include patients with a diagnosis of Crohn's disease, ulcerative colitis or IBD unclassified established at least 3 months prior to enrollment.A total of 10,206 patients were enrolled between March 2016 and April 2019, including 6,169 (60.4%) patients with Crohn's disease, 3,853 (37.8%) with ulcerative colitis, and 184 (1.8%) with a diagnosis of IBD unclassified. Thirty-two percent of patients were receiving AZA/thiopurines, 4.6% 6-mercaptopurine, and 3.2% methotrexate at study entry. At inclusion, 47.3% of patients were treated with an anti-tumor necrosis factor agent, 8.8% with vedolizumab, and 3.4% with ustekinumab. Roughly one quarter of patients (26.8%) underwent prior IBD related surgery. Sixty-six % of patients had been previously treated with systemic steroids. Three percent of patients had a medical history of cancer prior to inclusion, and 1.1% had a history of colonic, esophageal or uterine cervix high-grade dysplasia.I-CARE is an ongoing investigator-initiated observational European prospective cohort study that will provide unique information on the long-term benefits and risks of biological therapies in IBD patients

Prolyl hydroxylase-1 regulates hepatocyte apoptosis in an NF-kB-dependent manner

Hepatocyte death is an important contributing factor in a number of diseases of the liver. PHD1 confers hypoxic sensitivity upon transcription factors including the hypoxia inducible factor (HIF) and nuclear factor-kappaB (NF-κB). Reduced PHD1 activity is linked to decreased apoptosis. Here, we investigated the underlying mechanism(s) in hepatocytes. Basal NF-κB activity was elevated in PHD1(-/-) hepatocytes compared to wild type controls. ChIP-seq analysis confirmed enhanced binding of NF-κB to chromatin in regions proximal to the promoters of genes involved in the regulation of apoptosis. Inhibition of NF-κB (but not knock-out of HIF-1 or HIF-2) reversed the anti-apoptotic effects of pharmacologic hydroxylase inhibition. We hypothesize that PHD1 inhibition leads to altered expression of NF-κB-dependent genes resulting in reduced apoptosis. This study provides new information relating to the possible mechanism of therapeutic action of hydroxylase inhibitors that has been reported in pre-clinical models of intestinal and hepatic disease.status: publishe

Creation of micro-topographic features: a new tool for introducing specialist species of calcareous grassland to restored sites?

Questions: What types of pre-sowing disturbance are most suitable to establish specialist forbs of calcareous grassland at previously agriculturally improved restored sites? What impact does management regime have on post-establishment abundance-dynamics? Location: Pegsdon Hills, Bedfordshire, UK. Methods: We set up a 4-yr experiment using a split-plot design to combine pre-sowing disturbance treatments at sub-plot level (undisturbed control, glyphosate spraying, harrowing, and creation of ridge-and-furrow features) with three post-establishment management regimes applied at main plot level in years 2–4, involving either summer cutting or summer cattle grazing, and presence or absence of spring sheep grazing, along with autumn cattle grazing in all regimes. After disturbance application, we sowed a seed mixture containing ten specialist species of calcareous grassland. Using quadrat-based methods, we monitored first-year establishment and subsequent dynamics, including reproductive status of species at quadrat level. Initial establishment and subsequent dynamics were analysed separately using LMM. Results: Initial establishment of sown species was promoted both by harrowing and by ridge-and-furrow creation. While some species were about equally promoted by both, several other species benefited more strongly or exclusively from ridge-and-furrow creation. Effects of disturbance largely persisted in subsequent years, but for some species, different dynamics were observed for harrowed and ridge-and-furrow treatments. Thymus pulegioides and Hippocrepis comosa gradually achieved higher abundances in the ridge-and-furrow treatment, in which notable levels of bare ground persisted for much longer than in the harrowed treatment. In contrast, Filipendula vulgaris and Pimpinella saxifraga achieved higher abundance in the harrowed treatment. Sown species tended to reach reproductive stage faster in the ridge-and-furrow treatment than in the harrowed treatment. By the end of the study, management regimes had resulted in few effects on species dynamics. Conclusions: Establishment of specialist species of calcareous grassland crucially depended on bare ground creation prior to sowing. Ridge-and-furrow creation resulted in more persistent reduction of competition than the standard practice of harrowing, provided more suitable conditions for low-statured specialist species, and generally enabled faster transition of introduced specialist species to reproductive stage. Our results thus illustrate potential benefits of using more severe disturbance when introducing specialist species of calcareous grassland at restored sites