Synthetic Routes to a Library of Novel Methionine Synthase Inhibitors

Fungal infections are of continuous concern, especially with regard to immunocompromised patients. In an effort to develop new potential anti-fungal agents, we have begun synthesizing a library of potential inhibitors of the fungal Methionine Synthase (MetSyn) enzyme. Key differences between the B12-independant fungal MetSyn enzyme and the B12-dependant mammalian form can allow for an antifungal drug to be developed to exclusively bind the fungal enzyme and inhibit fungal growth while leaving the host (patient) unaffected. We are currently exploring the synthesis of various pterin and deazaguanine-based molecules as these mimic folate, an essential substrate for MetSyn function. We have begun testing these new molecules for activity in a fungal growth assay, as well as a fluorescent assay for monitoring MetSyn activity

Memory for Imagined Relationships and the Connection between Fantasy Orientation and Social Ability

Creating imaginary companions (ICs) is a common occurrence in early childhood. However, how often ICs are remembered beyond early childhood and what factors might influence that memory is an open question. Similarly, although having an IC in early childhood is associated with greater social ability; whether fantasy orientation is related to social ability later in life is unknown. I interviewed adolescents who participated in a study about ICs when they were preschoolers about their memories of those ICs. I predicted that the age at which a child created an IC, the duration of that IC, family support of the companion and the presence of a notable event related to the IC would influence whether adolescents remembered having an IC. I hypothesized that family support of an IC could be a proxy for family support of fantasy and that support of fantasy would be positively associated with fantasy orientation in adolescence. I also hypothesized that current fantasy orientation would be positively associated with Theory of Mind ability. About half of the adolescents interviewed remembered their childhood IC. Duration was positively associated with memory for ICs, while family support of an IC was marginally associated with memory. Neither family support nor having a notable event related to an IC was associated with adolescent fantasy orientation. Fantasy orientation and Theory of Mind ability were not correlated. The findings of this study suggest that many people do not remember their ICs from early childhood, but that longer duration and familial rehearsal may support recollection. In addition, the connection between fantasy and imaginative play and social ability seen in early childhood does not appear to persist into adolescence

Explaining intuitive difficulty judgments by modeling physical effort and risk

The ability to estimate task difficulty is critical for many real-world decisions such as setting appropriate goals for ourselves or appreciating others' accomplishments. Here we give a computational account of how humans judge the difficulty of a range of physical construction tasks (e.g., moving 10 loose blocks from their initial configuration to their target configuration, such as a vertical tower) by quantifying two key factors that influence construction difficulty: physical effort and physical risk. Physical effort captures the minimal work needed to transport all objects to their final positions, and is computed using a hybrid task-and-motion planner. Physical risk corresponds to stability of the structure, and is computed using noisy physics simulations to capture the costs for precision (e.g., attention, coordination, fine motor movements) required for success. We show that the full effort-risk model captures human estimates of difficulty and construction time better than either component alone

Synthetic Routes to a Library of Novel Methionine Synthase Inhibitors

Fungal infections are of continuous concern, especially with regard to immunocompromised patients. In an effort to develop new potential anti-fungal agents, we have begun synthesizing a library of potential inhibitors of the fungal Methionine Synthase (MetSyn) enzyme. Key differences between the B12-independant fungal MetSyn enzyme and the B12-dependant mammalian form can allow for an antifungal drug to be developed to exclusively bind the fungal enzyme and inhibit fungal growth while leaving the host (patient) unaffected. We are currently exploring the synthesis of various pterin and deazaguanine-based molecules as these mimic folate, an essential substrate for MetSyn function. We have begun testing these new molecules for activity in a fungal growth assay, as well as a fluorescent assay for monitoring MetSyn activity

Sodium oxybate therapy provides multidimensional improvement in fibromyalgia: results of an international phase 3 trial

Background: Fibromyalgia is characterised by chronic musculoskeletal pain and multiple symptoms including fatigue, multidimensional function impairment, sleep disturbance and tenderness. Along with pain and fatigue, non-restorative sleep is a core symptom of fibromyalgia. Sodium oxybate (SXB) is thought to reduce non-restorative sleep abnormalities. This study evaluated effects of SXB on fibromyalgia-related pain and other symptoms. Methods: 573 patients with fibromyalgia according to 1990 American College of Rheumatology criteria were enrolled at 108 centres in eight countries. Subjects were randomly assigned to placebo, SXB 4.5 g/night or SXB 6 g/night. The primary efficacy endpoint was the proportion of subjects with ≥30% reduction in pain visual analogue scale from baseline to treatment end. Other efficacy assessments included function, sleep quality, effect of sleep on function, fatigue, tenderness, health-related quality of life and subject's impression of change in overall wellbeing. Results: Significant improvements in pain, sleep and other symptoms associated with fibromyalgia were seen in SXB treated subjects compared with placebo. The proportion of subjects with ≥30% pain reduction was 42.0% for SXB4.5 g/night (p=0.002) and 51.4% for SXB6 g/night (p<0.001) versus 26.8% for placebo. Quality of sleep (Jenkins sleep scale) improved by 20% for SXB4.5 g/night (p≤0.001) and 25% for SXB6 g/night (p≤0.001) versus 0.5% for placebo. Adverse events with an incidence ≥5% and twice placebo were nausea, dizziness, vomiting, insomnia, anxiety, somnolence, fatigue, muscle spasms and peripheral oedema. Conclusion: These results, combined with findings from previous phase 2 and 3 studies, provide supportive evidence that SXB therapy affordsimportant benefits across multiple symptoms in subjects with fibromyalgia

The impact of lockdown during the COVID-19 outbreak on dietary habits in various population groups: A scoping review

Background: Since the beginning of the COVID-19 pandemic, access to fresh food has been restricted, and people are spending more time inside and have limited their physical activity. However, more time at home may have resulted in some positive habits including an increase in cooking. The aim of this review was to assess dietary changes during the first lockdown. Themes and patterns were considered and associations with other lifestyle factors were assessed. Methods: Between June and July 2020, the PubMed, Google Scholar, and Science Direct databases were searched, and results were screened for eligibility based on title, abstract, and full text. The inclusion criteria of this search included: papers published (or in pre-print) in the year 2020; studies that investigated the impact of COVID-19 lockdown on diet; papers published in English. Exclusion criteria were as follows: papers examining dietary changes in those following a structured diet based on diagnosed conditions or dietetic advice; literature, systematic, or narrative studies reviewing previous research. Researchers agreed on the study characteristics for extraction from final papers. Results: Four thousand three hundred and twenty-two studies were originally considered with 23 final full-text papers included. Four themes were identified: dietary patterns, dietary habits (favorable), dietary habits (unfavorable), and other (includes physical activity levels, weight gain). A total of 10 studies reported an increase in the number of snacks consumed, while six studies found that participants increased their meal number and frequency during quarantine. Eleven studies reported favorable changes in dietary habits with an increase in fresh produce and home cooking and reductions in comfort food and alcohol consumption. However, nine studies found a reduction in fresh produce, with a further six reporting an increase in comfort foods including sweets, fried food, snack foods, and processed foods. Two studies reported an increase in alcohol consumption. In eight studies participants reported weight gain with seven studies reporting a reduction in physical exercise. Conclusion: The effect of COVID-19 lockdown both negatively and positively impacted dietary practices throughout Europe and globally, and negative diet habits were associated with other poor lifestyle outcomes including weight gain, mental health issues, and limited physical activity. Both in the short term and if sustained in the long term, these changes may have significant impacts on the health of the population

Flamingo Vol. II N 2

Keeler, Clyde. Dad\u27s Day . Picture. 0. Puppet. Untitled. Prose. 1. Crescent. Untitled. Prose. 1. Williams, Charles L. As To Reading Biography . Prose. 5. Verlaine, Paul. Kyrie Eleison . Poem. 6. Anonymous. Mystery . Poem. 6. R. To You . Poem. 7. Q. The Passion Flower . Poem. 7. Bennett, G.W. November . Poem. 7. R. Storm . Poem. 7. Anonymous. Untitled.Prose. 8. Anonymous. No Doubt! . Poem. 8. Anonymous. Untitled. Picture. 8. McCutcheon, Dorothy. Ready-Made Reputations . Prose. 9. Anonymous. Untitled. Prose. 9. Anonymous. Untitled. Prose. 10. Ubersax, Delmar. Untitled. Prose. 10. Anonymous. Statistics From The Football Centers . Prose. 10. Anonymous. Our Own Handbook . Prose. 11. Anonymous. Real Reels . Prose. 12. Anonymous. Tire Trouble at The Round Table . Prose. 12. Anonymous. Untitled. Prose. 14. Anonymous. The Return From Dayton . Cartoon. 16. Anonymous. Untitled. Prose. 18. Anonymous. Down The Street . Poem. 18. Anonymous. The 7:30 . Poem. 18. Lord Jeff. In The Hole . Poem. 18. Anonymous. How It\u27s Done . Prose. 19. Anonymous. A Zoological Dream . Picture. 19. Anonymous. A Smooth Line . Prose. 20. Anonymous. Untitled. Prose. 20. Anonymous. You\u27ve Heart it . Prose. 20. Anonymous. Dog Gone! . Prose. 21. Anonymous. Untitled. Prose. 21. Cols Dis. Untitled. Poem. 21. Anonymous. Eddie Tor\u27s Lament . Poem. 22. Anonymous. Untitled. Prose. 22. Anonymous. The Long And Short of it. Prose. 22. Anonymous. Final Exam. In Zetetic Jactation 613 (You Look it up.) . Prose. 24. Pope of Fools. Love Letters of a Sceptic . Prose. 25. Anonymous. Untitled. Prose. 26. Williams, Grace. Untitled. Picture. 28. Anonymous. Untitled. Prose. 28. Goblin. It is a Wise Landlady . Prose. 28. Anonymous. Untitled. Prose. 28. Drexard. Untitled. Prose. 29. Chaparral. Untitled. Prose. 29. Punch Bowl. The Trifler . Prose. 29. Anonymous. His Finger Got Stuck in the Bowling Ball . Picture. 30. Chaparral. Untitled. Prose. 30. Banter. Untitled. Prose. 30. Tiger. Untitled. Prose. 30. Brown Jug. Untitled. Prose. 31. Octopus. Untitled. Prose. 31. Burr. Untitled. Prose. 31. Squib. Untitled. Prose. 31. Ubersax, Delmar. Untitled. Picture. 32. Purple Cow. Untitled. Prose. 32. Mather, William G. A Ditty . Poem. 12