Inhibition of HIV replication by amino-sugar derivatives

AbstractThe plant alkaloids castanospermine, dihydroxymethyldihydroxypyrrolidine and deoxynojirimycin have recently been shown to have potential anti-HIV activity [(1987) Proc. Natl. Acad. Sci. USA 84, 8120–8124; (1987) Nature 330, 74–77; (1987) Lancet i, 1025–1026]. They are thought to act by inhibiting α-glucosidase I, an enzyme involved in the processing of N-linked oligosaccharides on glycoproteins. We report here the relative efficacy of a spectrum of amino-sugar derivatives as inhibition of HIV cytopathicity. Several α-glucosidase inhibitors and α-fucosidase inhibitors were found to be active at concentrations which were non-cytotoxic

Football fans in training: the development and optimization of an intervention delivered through professional sports clubs to help men lose weight, become more active and adopt healthier eating habits

<p>Background: The prevalence of obesity in men is rising, but they are less likely than women to engage in existing weight management programmes. The potential of professional sports club settings to engage men in health promotion activities is being increasingly recognised. This paper describes the development and optimization of the Football Fans in Training (FFIT) programme, which aims to help overweight men (many of them football supporters) lose weight through becoming more active and adopting healthier eating habits.</p> <p>Methods: The MRC Framework for the design and evaluation of complex interventions was used to guide programme development in two phases. In Phase 1, a multidisciplinary working group developed the pilot programme (p-FFIT) and used a scoping review to summarize previous research and identify the target population. Phase 2 involved a process evaluation of p-FFIT in 11 Scottish Premier League (SPL) clubs. Participant and coach feedback, focus group discussions and interviews explored the utility/acceptability of programme components and suggestions for changes. Programme session observations identified examples of good practice and problems/issues with delivery. Together, these findings informed redevelopment of the optimized programme (FFIT), whose components were mapped onto specific behaviour change techniques using an evidence-based taxonomy.</p> <p>Results: p-FFIT comprised 12, weekly, gender-sensitised, group-based weight management classroom and ‘pitch-side’ physical activity sessions. These in-stadia sessions were complemented by an incremental, pedometer-based walking programme. p-FFIT was targeted at men aged 35-65 years with body mass index ≥ 27 kg/m2. Phase 2 demonstrated that participants in p-FFIT were enthusiastic about both the classroom and physical activity components, and valued the camaraderie and peer-support offered by the programme. Coaches appreciated the simplicity of the key healthy eating and physical activity messages. Suggestions for improvements that were incorporated into the optimized FFIT programme included: more varied in-stadia physical activity with football-related components; post-programme weight management support (emails and a reunion session); and additional training for coaches in SMART goal setting and the pedometer-based walking programme.</p> <p>Conclusions: The Football Fans in Training programme is highly acceptable to participants and SPL coaches, and is appropriate for evaluation in a randomised controlled trial.</p&gt

A blood atlas of COVID-19 defines hallmarks of disease severity and specificity.

Treatment of severe COVID-19 is currently limited by clinical heterogeneity and incomplete description of specific immune biomarkers. We present here a comprehensive multi-omic blood atlas for patients with varying COVID-19 severity in an integrated comparison with influenza and sepsis patients versus healthy volunteers. We identify immune signatures and correlates of host response. Hallmarks of disease severity involved cells, their inflammatory mediators and networks, including progenitor cells and specific myeloid and lymphocyte subsets, features of the immune repertoire, acute phase response, metabolism, and coagulation. Persisting immune activation involving AP-1/p38MAPK was a specific feature of COVID-19. The plasma proteome enabled sub-phenotyping into patient clusters, predictive of severity and outcome. Systems-based integrative analyses including tensor and matrix decomposition of all modalities revealed feature groupings linked with severity and specificity compared to influenza and sepsis. Our approach and blood atlas will support future drug development, clinical trial design, and personalized medicine approaches for COVID-19

The Anoka Focus

In 1936, the Lynch site, 25BDl, in North Central Nebraska was investigated by a party from the University of Nebraska under the qirection of Dr. Earl H. Bell. Preliminary estimates of age measured in many hundreds and even thousands of years created widespread interest. These data, with more conservative conclusions as to their ambiguity, were considered by Freed (1954) in her Master’s Thesis on file at the University of Nebraska. In 1939, the Arzberger site, 39HU6, near Pierre, South Dakota, was excavated by a party from Columbia University led by Albert C. Spaulding, under the general direction of the late Dr. W. D. Strong. The final report of this work was published by Spaulding in 1956. His statistical analysis of the artifacts, and the insights gained thereby, made a review of the earlier work by Freed, as well as further field work seem highly desirable. The field work was carried out in the summer of 1959, and the correlation of the results of that investigation with the earlier work by Spaulding, Freed, and others has continued since that time. The comparison of data gathered through investigation of archeological sites forms the basis for the identification and classification of prehistoric cultures. Within the literature of Plains Archeology, several different techniques of classification are found. Major systems such as Cultures (Strong, 1933; 271-287), Traditions (Lehmer, 1954; 140) and the Midwestern Taxonomic System (McKern, 1936; 7) have been used. The problem to be considered in this paper will be the comparison and ordering of archeological data from the Lynch, Arzberger, and other sites into such a comparative complex. The method to be followed is that of the Midwestern Taxonomic System. The primary level of classification to be demonstrated is the Focus. The basis for such identification will be the majority of shared traits found at the sites just mentioned. Attributes of time and space will be excluded from the Focus definition, as is required in the Midwestern Taxonomic System. The procedure to be followed in the Focus identification is: 1. A presentation of the traits from the Lynch site, 25BDl, as gathered from two seasons of excavations. 2. A summary description of traits from the Arzberger site, 39HU6, along with a review of data gathered from surface surveys at 25BD2, 25BD3, and 25BD4. 3. The identification of the Anoka Focus based upon the great majority of shared traits from the above sites. 4. A brief consideration of the Anoka Focus with other local manifestations in regard to time and space relationships. Note: Plates 1-14 were not available in the copy of the work from which this digital version was prepared. The compilers regret and apologize for this omission