Safety and physiological effects of two different doses of elosulfase alfa in patients with morquio a syndrome: A randomized, double-blind, pilot study.

The primary treatment outcomes of a phase 2, randomized, double-blind, pilot study evaluating safety, physiological, and pharmacological effects of elosulfase alfa in patients with Morquio A syndrome are herewith presented. Patients aged ≥7 years and able to walk ≥200 m in the 6-min walk test (6MWT) were randomized to elosulfase alfa 2.0 or 4.0 mg/kg/week for 27 weeks. The primary objective was to evaluate the safety of both doses. Secondary objectives were to evaluate effects on endurance (6MWT and 3-min stair climb test [3MSCT]), exercise capacity (cardio-pulmonary exercise test [CPET]), respiratory function, muscle strength, cardiac function, pain, and urine keratan sulfate (uKS) levels, and to determine pharmacokinetic parameters. Twenty-five patients were enrolled (15 randomized to 2.0 mg/kg/week and 10 to 4.0 mg/kg/week). No new or unexpected safety signals were observed. After 24 weeks, there were no improvements versus baseline in the 6MWT, yet numerical improvements were seen in the 3MSCT with 4.0 mg/kg/week. uKS and pharmacokinetic data suggested no linear relationship over the 2.0-4.0 mg/kg dose range. Overall, an abnormal exercise capacity (evaluated in 10 and 5 patients in the 2.0 and 4.0 mg/kg/week groups, respectively), impaired muscle strength, and considerable pain were observed at baseline, and there were trends towards improvements in all domains after treatment. In conclusion, preliminary data of this small study in a Morquio A population with relatively good endurance confirmed the acceptable safety profile of elosulfase alfa and showed a trend of increased exercise capacity and muscle strength and decreased pain

Recon 2.2: from reconstruction to model of human metabolism.

IntroductionThe human genome-scale metabolic reconstruction details all known metabolic reactions occurring in humans, and thereby holds substantial promise for studying complex diseases and phenotypes. Capturing the whole human metabolic reconstruction is an on-going task and since the last community effort generated a consensus reconstruction, several updates have been developed.ObjectivesWe report a new consensus version, Recon 2.2, which integrates various alternative versions with significant additional updates. In addition to re-establishing a consensus reconstruction, further key objectives included providing more comprehensive annotation of metabolites and genes, ensuring full mass and charge balance in all reactions, and developing a model that correctly predicts ATP production on a range of carbon sources.MethodsRecon 2.2 has been developed through a combination of manual curation and automated error checking. Specific and significant manual updates include a respecification of fatty acid metabolism, oxidative phosphorylation and a coupling of the electron transport chain to ATP synthase activity. All metabolites have definitive chemical formulae and charges specified, and these are used to ensure full mass and charge reaction balancing through an automated linear programming approach. Additionally, improved integration with transcriptomics and proteomics data has been facilitated with the updated curation of relationships between genes, proteins and reactions.ResultsRecon 2.2 now represents the most predictive model of human metabolism to date as demonstrated here. Extensive manual curation has increased the reconstruction size to 5324 metabolites, 7785 reactions and 1675 associated genes, which now are mapped to a single standard. The focus upon mass and charge balancing of all reactions, along with better representation of energy generation, has produced a flux model that correctly predicts ATP yield on different carbon sources.ConclusionThrough these updates we have achieved the most complete and best annotated consensus human metabolic reconstruction available, thereby increasing the ability of this resource to provide novel insights into normal and disease states in human. The model is freely available from the Biomodels database (http://identifiers.org/biomodels.db/MODEL1603150001)

Urban blue space renovation and local resident and visitor well-being:A case study from Plymouth, UK

Observational studies have suggested that people with better access to attractive, safe, and inclusive blue spaces enjoy higher psychological well-being, with particular benefits for those living in deprived urban areas. However, intervention studies are scarce. To help bridge this gap we conducted a repeat cross-sectional study exploring local resident and visitor well-being before and after a small-scale intervention aimed at improving the quality of an urban beach area in a deprived neighbourhood in Plymouth, United Kingdom. Physical alterations were co-created with local stakeholders and residents, and accompanied by a series of on-site community events. Key outcomes were self-reported psychological well-being, satisfaction with personal safety and community belonging, and perceptions of site quality. Adjusted linear models showed that positive well-being (B = 7.42; 95% CI = 4.18–10.67) and life satisfaction (B = 0.40; 95% CI = 0.11–0.70) were both higher after the intervention compared to before, with associations for life satisfaction stronger among those who visited the site in the last four weeks. Associations with positive well-being were partially mediated by greater satisfaction with community belonging; and associations with life satisfaction were partially and independently mediated by greater satisfaction with personal safety and community belonging. Although caution needs to be taken due to the repeat cross-sectional design and the sampling of site visitors as well as local residents, the findings support the idea that environmental improvements to urban blue spaces can foster better psychological well-being, and underline the importance of community involvement in the process

Using the community psychology competencies to address sexual assault on a college campus

Sexual assault on college campuses is a national issue, with a recent report from the White House estimating that 20% of women will experience a sexual assault during college.  Students at Wichita State University formed a campus organization to bring visibility to both community psychology and address this important problem.  The Community Psychology Association is comprised of both graduate and undergraduate students, and members utilized three community psychology competencies: ecological perspectives, information dissemination/building public awareness, and community organizing and community advocacy in their work to improve resources and campus support for this issue.  Community Psychology Association members utilized focus groups with campus students, faculty, and staff to facilitate discussions on sexual assault, campus safety, and university and administrative accountability.  Content analysis revealed multiple themes that were used to generate a larger campus discussion and promote change in campus policies. As a result of these activities, major changes occurred at Wichita State, including data driven programming for interventions regarding sexual assault, changes in leadership in the offices of Title IX and Student Affairs, support for a CDC grant, and overall increased organizational awareness for sexual assault survivors.  This study highlights the importance of applying community psychology principles and concepts to research and action to ultimately have a positive and tangible impact on the local community

Using the community psychology competencies to address sexual assault on a college campus

Sexual assault on college campuses is a national issue, with a recent report from the White House estimating that 20% of women will experience a sexual assault during college.  Students at Wichita State University formed a campus organization to bring visibility to both community psychology and address this important problem.  The Community Psychology Association is comprised of both graduate and undergraduate students, and members utilized three community psychology competencies: ecological perspectives, information dissemination/building public awareness, and community organizing and community advocacy in their work to improve resources and campus support for this issue.  Community Psychology Association members utilized focus groups with campus students, faculty, and staff to facilitate discussions on sexual assault, campus safety, and university and administrative accountability.  Content analysis revealed multiple themes that were used to generate a larger campus discussion and promote change in campus policies. As a result of these activities, major changes occurred at Wichita State, including data driven programming for interventions regarding sexual assault, changes in leadership in the offices of Title IX and Student Affairs, support for a CDC grant, and overall increased organizational awareness for sexual assault survivors.  This study highlights the importance of applying community psychology principles and concepts to research and action to ultimately have a positive and tangible impact on the local community

Short-Term Very High Carbohydrate Diet and Gut-Training Have Minor Effects on Gastrointestinal Status and Performance in Highly Trained Endurance Athletes

We implemented a multi-pronged strategy (MAX) involving chronic (2 weeks high carbohydrate [CHO] diet + gut-training) and acute (CHO loading + 90 g·h(−1) CHO during exercise) strategies to promote endogenous and exogenous CHO availability, compared with strategies reflecting lower ranges of current guidelines (CON) in two groups of athletes. Nineteen elite male race walkers (MAX: 9; CON:10) undertook a 26 km race-walking session before and after the respective interventions to investigate gastrointestinal function (absorption capacity), integrity (epithelial injury), and symptoms (GIS). We observed considerable individual variability in responses, resulting in a statistically significant (p < 0.001) yet likely clinically insignificant increase (Δ 736 pg·mL(−1)) in I-FABP after exercise across all trials, with no significant differences in breath H(2) across exercise (p = 0.970). MAX was associated with increased GIS in the second half of the exercise, especially in upper GIS (p < 0.01). Eighteen highly trained male and female distance runners (MAX: 10; CON: 8) then completed a 35 km run (28 km steady-state + 7 km time-trial) supported by either a slightly modified MAX or CON strategy. Inter-individual variability was observed, without major differences in epithelial cell intestinal fatty acid binding protein (I-FABP) or GIS, due to exercise, trial, or group, despite the 3-fold increase in exercise CHO intake in MAX post-intervention. The tight-junction (claudin-3) response decreased in both groups from pre- to post-intervention. Groups achieved a similar performance improvement from pre- to post-intervention (CON = 39 s [95 CI 15–63 s]; MAX = 36 s [13–59 s]; p = 0.002). Although this suggests that further increases in CHO availability above current guidelines do not confer additional advantages, limitations in our study execution (e.g., confounding loss of BM in several individuals despite a live-in training camp environment and significant increases in aerobic capacity due to intensified training) may have masked small differences. Therefore, athletes should meet the minimum CHO guidelines for training and competition goals, noting that, with practice, increased CHO intake can be tolerated, and may contribute to performance outcomes

Short-term very high carbohydrate diet and gut-training have minor effects on gastrointestinal status and performance in highly trained endurance athletes

We implemented a multi-pronged strategy (MAX) involving chronic (2 weeks high carbohydrate [CHO] diet + gut-training) and acute (CHO loading + 90 g·h−1 CHO during exercise) strategies to promote endogenous and exogenous CHO availability, compared with strategies reflecting lower ranges of current guidelines (CON) in two groups of athletes. Nineteen elite male race walkers (MAX: 9; CON:10) undertook a 26 km race-walking session before and after the respective interventions to investigate gastrointestinal function (absorption capacity), integrity (epithelial injury), and symptoms (GIS). We observed considerable individual variability in responses, resulting in a statistically significant (p < 0.001) yet likely clinically insignificant increase (Δ 736 pg·mL−1) in I-FABP after exercise across all trials, with no significant differences in breath H2 across exercise (p = 0.970). MAX was associated with increased GIS in the second half of the exercise, especially in upper GIS (p < 0.01). Eighteen highly trained male and female distance runners (MAX: 10; CON: 8) then completed a 35 km run (28 km steady-state + 7 km time-trial) supported by either a slightly modified MAX or CON strategy. Inter-individual variability was observed, without major differences in epithelial cell intestinal fatty acid binding protein (I-FABP) or GIS, due to exercise, trial, or group, despite the 3-fold increase in exercise CHO intake in MAX post-intervention. The tight-junction (claudin-3) response decreased in both groups from pre- to post-intervention. Groups achieved a similar performance improvement from pre- to post-intervention (CON = 39 s [95 CI 15–63 s]; MAX = 36 s [13–59 s]; p = 0.002). Although this suggests that further increases in CHO availability above current guidelines do not confer additional advantages, limitations in our study execution (e.g., confounding loss of BM in several individuals despite a live-in training camp environment and significant increases in aerobic capacity due to intensified training) may have masked small differences. Therefore, athletes should meet the minimum CHO guidelines for training and competition goals, noting that, with practice, increased CHO intake can be tolerated, and may contribute to performance outcomes

A database of microRNA expression patterns in Xenopus laevis

MicroRNAs (miRNAs) are short, non-coding RNAs around 22 nucleotides long. They inhibit gene expression either by translational repression or by causing the degradation of the mRNAs they bind to. Many are highly conserved amongst diverse organisms and have restricted spatio-temporal expression patterns during embryonic development where they are thought to be involved in generating accuracy of developmental timing and in supporting cell fate decisions and tissue identity. We determined the expression patterns of 180 miRNAs in Xenopus laevis embryos using LNA oligonucleotides. In addition we carried out small RNA-seq on different stages of early Xenopus development, identified 44 miRNAs belonging to 29 new families and characterized the expression of 5 of these. Our analyses identified miRNA expression in many organs of the developing embryo. In particular a large number were expressed in neural tissue and in the somites. Surprisingly none of the miRNAs we have looked at show expression in the heart. Our results have been made freely available as a resource in both XenMARK and Xenbase

A Novel Method for Measuring the Burden of Breast Cancer in Neighborhoods

Community-based breast cancer prevention efforts often focus on women who live in the same neighborhoods, as they tend to have similar demographic characteristics, health behaviors, and environmental exposures; yet little research describes methods of selecting neighborhoods of focus for community-based cancer prevention interventions. Studies frequently use demographics from census data, or single breast cancer outcomes (e.g., mortality, morbidity) in order to choose neighborhoods of focus for breast cancer interventions, which may not be optimal. This study presents a novel method for measuring the burden of breast cancer among neighborhoods that could be used for selecting neighborhoods of focus. In this study, we 1) calculate a metric composed of multiple breast cancer outcomes to describe the burden of breast cancer in census tracts Philadelphia, PA, USA; 2) map the neighborhoods with the greatest breast cancer burden; and 3) compare census tracts with the highest burden of breast cancer to those with demographics sometimes used for geo-based prioritization, i.e., race and income. The results of our study showed that race or income may not be appropriate proxies for neighborhood breast cancer burden; comparing the breast cancer burden with demographics at the census tract level, we found few overlaps with the highest percentage African American or the lowest median incomes. Agencies implementing community-based breast cancer interventions should consider this method to inform the selection of neighborhoods for breast cancer prevention interventions, including education, screening, and treatment